bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic Analysis of Liquor Starter Culture Revealed Beneficial Microbes’ Presence
Authors: Din Ahmad Ud , Ahmad Waqar , Khan Taj Malook , Wang Jun , Wu Jianbo
Published: December 2022

Wines are complex matrices famous for their pleasant aroma and exceptional flavor. Baijiu (white wine) is a traditional Chinese liquor with a soft mouthfeel, fragrant taste, and long-lasting aftertaste. Baijiu is distilled from sorghum and wheat via solid fermentation. As in wines, the microbial ecosystem of Baijiu is a key decisive factor influencing aroma and consumer preferences. Microbial diversity in Baijiu has been intensively investigated. It is important to note that probiotics are a mixture of bacteria and yeast primarily intended to improve health. Our study aimed to characterize the microbial ecosystem of Zaopei Baijiu Daqu (ZBD) starter cultures for specific microbes with probiotic properties. The DNA samples of ZBD starters were analyzed using a metagenomic 16S rRNA approach to characterize the bacterial and ITS for fungal diversity. Weissella cibaria was the most dominant species in the bacterial community, while Saccharomycopsis fibuligera was the most abundant fungal species. Furthermore, functional prediction analysis identified unique pathways associated with microbial diversity relevant to functional innovation. These associated pathways include fermentation, amino acid metabolism, carbohydrate metabolism, energy metabolism, and membrane transport. This study identified beneficial microbes in the starter culture, opening a path for further in-depth analysis of those microbes by isolating and evaluating them for a valuable role in in vitro and in vivo studies.
Defining Cyber Risk Scenarios to Evaluate IoT Systems
Authors: Andrade Roberto , Ortiz Iván , Cazares María , Navas Gustavo , Sánchez-Pazmiño María Isabel
Published: December 2022

The growth of the Internet of Things (IoT) has accelerated digital transformation processes in organizations and cities. However, it has also opened new security challenges due to the complexity and dynamism of these systems. The application of security risk analysis methodologies used to evaluate information technology (IT) systems have their limitations to qualitatively assess the security risks in IoT systems, due to the lack of historical data and the dynamic behavior of the solutions based on the IoT. The objective of this study is to propose a methodology for developing a security risk analysis using scenarios based on the risk factors of IoT devices. In order to manage the uncertainty due to the dynamics of IoT behaviors, we propose the use of Bayesian networks in conjunction with the Best Worst Method (BWM) for multi-criteria decision-making to obtain a quantitative security risk value.
The Role of Pancreatic Fatty Acid Synthesis in Islet Morphology and Function after Caloric Restriction or Roux-En-Y Gastric Bypass Surgery in Mice
Authors: Mo Haocong , Liu Yang , Zhang Mengyuan , Qiu Zirui , Li Yilin , Zhang Zhejiao , Li Yanting , Xu Geyang
Published: December 2022

Background: Both caloric restriction (CR) and Roux-en-Y gastric bypass (RYGB) are practical interventions for type 2 diabetes mellitus (T2DM), while the molecular mechanisms of CR and RYGB regarding glycemic control are still poorly understood. Here, we explore the effects and underlying mechanisms of CR and RYGB on β-cell area and function. Methods: Average islet size was measured by histological analysis. The pancreatic lipid content was detected by using a commercial lipid assay kit. The expression levels of lipogenic transcription factors and enzymes in mouse pancreas were determined by quantitative PCR, Western blot, and immunofluorescence. Results: CR decreased the mean size of islets and pancreatic insulin production in both regular diet-fed and high-fat diet-fed mice. Increased β-cell apoptosis was detected in the calorie-restricted mice. Interestingly, the lipogenic transcription factors and enzymes such as SREBP1c, PPARγ, FASN and ACC were upregulated in the pancreas after CR. In contrast to CR, RYGB decreased the apoptosis of β-cells and the expression of fatty acid synthase. Conclusions: Pancreatic fatty acid synthesis is critical to the β-cell function after CR and RYGB.
Genome-Wide Analysis of Specific PfR2R3-MYB Genes Related to Paulownia Witches’ Broom
Authors: Zhao Xiaogai , Li Bingbing , Zhai Xiaoqiao , Liu Haifang , Deng Minjie , Fan Guoqiang
Published: December 2022

Paulownia witches’ broom (PaWB), caused by phytoplasmas, is the most devastating infectious disease of Paulownia. R2R3-MYB transcription factors (TF) have been reported to be involved in the plant’s response to infections caused by these pathogens, but a comprehensive study of the R2R3-MYB genes in Paulownia has not been reported. In this study, we identified 138 R2R3-MYB genes distributed on 20 chromosomes of Paulownia fortunei. These genes were classified into 27 subfamilies based on their gene structures and phylogenetic relationships, which indicated that they have various evolutionary relationships and have undergone rich segmental replication events. We determined the expression patterns of the 138 R2R3-MYB genes of P. fortunei by analyzing the RNA sequencing data and found that PfR2R3-MYB15 was significantly up-regulated in P. fortunei in response to phytoplasma infections. PfR2R3-MYB15 was cloned and overexpressed in Populus trichocarpa. The results show that its overexpression induced branching symptoms. Subsequently, the subcellular localization results showed that PfR2R3-MYB15 was located in the nucleus. Yeast two-hybrid and bimolecular fluorescence complementation experiments showed that PfR2R3-MYB15 interacted with PfTAB2. The analysis of the PfR2R3-MYB15 gene showed that it not only played an important role in plant branching, but also might participate in the biosynthesis of photosystem elements. Our results will provide a foundation for future studies of the R2R3-MYB TF family in Paulownia and other plants.
Pharmacological Treatment of Type-2-Diabetes and Cardiovascular Comorbidities: Differences between Undocumented Migrants and Natives in Italy
Authors: Fiorini Gianfrancesco , Pellegrini Giacomo , Franchi Matteo , Pincelli Angela Ida , Rigamonti Antonello Emilio , Corrao Giovanni , Sartorio Alessandro , Cella Silvano Gabriele
Published: December 2022

Diabetes prevalence is growing worldwide, especially in some populations. Though migrations seem to contribute to the presence in host countries of a significant number of patients with diabetes and its comorbidities, very little is known about the health conditions of undocumented migrants. We retrospectively studied 838 patients with type 2 diabetes mellitus (T2DM), 425 Italians followed by the diabetes clinic of a university hospital, and 413 undocumented migrants receiving assistance from a non-governmental organization. We analyzed their demographic and clinical data together with the medications they were on. The prevalence of the use of specific classes of drugs was compared between undocumented migrants and Italians by fitting a Poisson regression model, and the results were reported as prevalence rate ratios (PRRs) with a 95% confidence interval. Undocumented migrants with T2DM received fewer medications for cardiovascular (CV) conditions (PRR: 0.68, 0.60 to 0.76) than Italians, after correcting for confounding factors. Only sulfonylureas were more frequently used in undocumented migrants. The causes of these differences are not completely clear, but social, cultural, and economic factors can have an important role. More efforts are needed to provide appropriate treatment of diabetes and its CV comorbidities to undocumented migrants.
Historical Osteopathic Principles and Practices in Contemporary Care: An Anthropological Perspective to Foster Evidence-Informed and Culturally Sensitive Patient-Centered Care: A Commentary
Authors: Zegarra-Parodi Rafael , Baroni Francesca , Lunghi Christian , Dupuis David
Published: December 2022

Historical osteopathic principles and practices (OPP)—considering the patient as a dynamic interaction of the body, mind, and spirit and incorporating the body’s self-healing ability into care—are inherited from traditional/complementary and alternative (CAM) principles. Both concepts are familiar to contemporary osteopathic practitioners, but their incorporation into healthcare for evidence-informed, patient-centered care (PCC) remains unclear. Further, a polarity exists in the osteopathic profession between a ‘traditional-minded’ group following historical OPP despite evidence against those models and an ‘evidence-minded’ group following the current available evidence for common patient complaints. By shifting professional practices towards evidence-based practices for manual therapy in line with the Western dominant biomedical paradigm, the latter group is challenging the osteopathic professional identity. To alleviate this polarity, we would like to refocus on patient values and expectations, highlighting cultural diversity from an anthropological perspective. Increasing an awareness of diverse sociocultural health assumptions may foster culturally sensitive PCC, especially when including non-Western sociocultural belief systems of health into that person-centered care. Therefore, the current medical anthropological perspective on the legacy of traditional/CAM principles in historical OPP is offered to advance the osteopathic profession by promoting ethical, culturally sensitive, and evidence-informed PCC in a Western secular environment. Such inclusive approaches are likely to meet patients’ values and expectations, whether informed by Western or non-Western sociocultural beliefs, and improve their satisfaction and clinical outcomes.
Intentional Replantation of Single-Rooted and Multi-Rooted Teeth: A Systematic Review
Authors: Pisano Massimo , Di Spirito Federica , Martina Stefano , Sangiovanni Giuseppe , D’Ambrosio Francesco , Iandolo Alfredo
Published: December 2022

The technique of intentional replantation can provide a second chance to save teeth that would be destined for extraction. Therefore, the present systematic review aimed primarily to estimate tooth survival after intentional replantation and secondarily to compare treatment outcomes in single-rooted and multi-rooted teeth. The study protocol was developed before the analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Articles were electronically searched in PubMed/MEDLINE, the COCHRANE library and Google Scholar by two independent reviewers, and those that met the eligibility criteria were included. A statistical analysis using the chi-square test with a p-value of <0.05 was performed on the reported outcomes of intentional replantation. A total of 44 single-rooted replanted teeth with five failures (11.36%) and 42 multi-rooted replanted teeth with six failures (14.28%) were reported in the literature, corresponding to a survival rate of 88.64% and 85.57%, respectively. The overall survival rate for the replantation procedure was 86.7%, indicating that intentional replantation can be considered a safe therapeutic choice, with no statistically significant difference between the survival rates of single-rooted and multi-rooted replanted teeth.
Adverse Effects of Smartphone Addiction among University Students in South Korea: A Systematic Review
Authors: Achangwa Chiara , Ryu Hyun Sik , Lee Jae Kwang , Jang Ju-Dong
Published: December 2022

Background: Globally there has been an exponential increase in the penetration of smartphones among the youth population and smartphones have become indispensable in the daily lives of university students in South Korea. Several studies have associated the problematic use of smartphones or addiction with different adverse outcomes. The goal of this study was to collate empirical evidence and provides an overall synthesis of the literature about the adverse effects of smartphone addiction on university students in South Korea. Method: We carried out a systematic review of the published literature between August and October 2022 on the adverse effects of smartphone addiction on university students in South Korea, published between 2012 and 2022 in Pubmed/Medline, PsycInfo, Embase, Biomed-Central, Web of Science, Directory of Open Access Journals, Elsevier’s collection, Wiley Online Library, SpringerLink, Sage Journal’s collection and Cochrane Library. Results: Thirty-four articles published between 2012 and 2022 were included in the synthesis of this review. Eight studies explored the association between smartphone addiction and the psychological and mental health of university students in Korea. Smartphone addiction was associated with physical health leading to sleep disorders and musculoskeletal and neurological problems. Academic performance, procrastination, impulsivity, self-esteem, reduced social interaction, solitude, and suicide were also negatively associated with smartphone addiction. Conclusions: Our study adds to the literature regarding the adverse effects of smartphone addiction on university students in Korea and provides more information for addiction prevention and health promotion activities.
Volume–Outcome Relationship in Cancer Survival Rates: Analysis of a Regional Population-Based Cancer Registry in Japan
Authors: Sato Yoichiro , Kaneko Rena , Yano Yuichiro , Kamada Kentaro , Kishimoto Yuui , Ikehara Takashi , Sato Yuzuru , Matsuda Takahisa , Igarashi Yoshinori
Published: December 2022

Background: There is limited data on the relationship between hospital volumes and outcomes with respect to cancer survival in Japan. The primary objective of this study was to evaluate the effect of hospital volume on cancer survival rate using a population-based cohort database. Methods: Using the Kanagawa cancer registry, propensity score matching was employed to create a dataset for each cancer type by selecting 1:1 matches for cases from high- and other-volume hospitals. The 5-year survival rate was estimated and the hazard ratio (HR) for hospital volume was calculated using a Cox proportional hazard model. Additional analyses were performed limited to cancer patients who underwent surgical operation, chemotherapy, and other treatments in each tumor stage and at the time of diagnosis. Results: The number of cases with complete data, defined as common cancers (prostate, kidney, bladder, esophagus, stomach, liver, pancreas, colon, breast, and lung), was 181,039. Adjusted HR differed significantly among hospital volume categories for the most common cancers except bladder, and the trends varied according to cancer type. The HR ranged from 0.76 (95%CI, 0.74–0.79) for stomach cancer to 0.85 (0.81–0.90) for colon cancer. Conclusions: This study revealed that a relationship may exist between hospital volume and cancer survival in Japan.
Drought Stress in Horticultural Plants
Authors: Toscano Stefania , Franzoni Giulia , Álvarez Sara
Published: December 2022

Drought stress is one of the main factors limiting horticultural crops, especially in environments such as the Mediterranean basin, which is often characterized by sub-optimal water availability [...]
Double Disadvantage of Carers with a Disability: A Cross-Sectional Study of Care Duration and Perceived Importance for Service Improvement in Hong Kong, China
Authors: Chan Wai , Xin Meiqi , Lu Erin Yiqing , Cheung Wai Ming , Tsang Hector Wing Hong
Published: December 2022

Objectives: this study examined (i) the relationships between the care duration of carers and their perceptions of the importance of service improvement by types of service, and (ii) whether carers had a disability that moderated the impacts of care duration on these perceptions. Design: survey data for cross-sectional analyses. Method: The sample consisted of carers without disability (n = 625) and carers with a disability (n = 77). Hierarchical multiple regression was applied to examine the unique contribution of care duration. The interaction effects of the disability status of the carer was also estimated. Results: Longer care duration was associated with a greater perception of the importance of service improvement for certain services by carers. The positive relationships between care duration and perception of the importance of caregiver assistances and financial subsidy improvement were stronger for carers with disabilities compared to carers without disability. Conclusions: Long-term carers with disabilities face a potential double disadvantage of service improvement needs with more years of caregiving. Policy makers should consider prioritizing caregiver assistances or financial subsidy service improvements for long-term carers who themselves have a disability.
How Can Music Engagement Address Loneliness? A Qualitative Study and Thematic Framework in the Context of Australia’s COVID-19 Pandemic Lockdowns
Authors: Kiernan Frederic , Davidson Jane W.
Published: December 2022

Social isolation and loneliness are serious public health concerns. Music engagement can strengthen social connections and reduce loneliness in some contexts, although how this occurs is not well understood; research suggests that music’s capacity to manipulate perceptions of time and space is relevant. This study adopted a qualitative perspective to examine how music engagement shaped the experiences of residents of Victoria, Australia, during conditions of restricted social contact during the lockdowns of 2020. Semi-structured interviews explored participants’ lived musical experiences while giving focus to perceptions of time and space (e.g., how music helped restructure home and workspaces in response to lockdown regulations, or punctuate time where older routines were no longer viable). Interpretative Phenomenological Analysis of the interview transcripts identified five themes representing the key findings: (1) a super-ordinate theme of perceived control, which comprises four themes: (2) dynamic connection; (3) identity; (4) mobility; (5) presence. Each theme describes one generalised aspect of the way music engagement shaped participants’ perceptions of time and space during lockdown and supported their processes of adaptation to and coping with increased social isolation. The authors argue that these findings may inform the way music can be used to address loneliness in everyday life.
The Mediating Role of Sleep Quality in the Relationship between Negative Emotional States and Health-Related Quality of Life among Italian Medical Students
Authors: Carpi Matteo , Vestri Annarita
Published: December 2022

Sleep problems have been shown to be related to adverse outcomes concerning physical and mental well-being. Furthermore, mental health issues and sleep problems were reported to be highly prevalent among medical students and physicians, and were found to be associated with worse academic and clinical performance in these populations. This study aims to investigate the prevalence of poor sleep to examine the associations between sleep quality and health-related quality of life (HRQoL), and to explore the possible mediating role of sleep in the relationship between psychological distress and HRQoL itself in a sample of medical and dental students attending a large Italian university. Participants (n = 407, mean age: 24.2 ± 2.4) answered an online questionnaire comprising the 21-item Depression Anxiety Stress Scale, the Pittsburgh Sleep Quality Index, and the Short Form-12 health survey. Up to 62% of the participants reported poor sleep quality. Controlling for psychological distress, sleep quality components were found to be associated with physical and mental HRQoL. Mediation analysis showed that overall sleep quality mediated all the single associations between anxiety, depression, and stress and HRQoL. These preliminary findings suggest that the quality of sleep is important for the well-being of medical students and that targeting sleep issues in this academic population may be beneficial.
New Approach to Modelling the Impact of Heavy Metals on the European Union’s Water Resources
Authors: Zlati Monica Laura , Georgescu Lucian Puiu , Iticescu Catalina , Ionescu Romeo Victor , Antohi Valentin Marian
Published: December 2022

The present research aims to address the highly topical issue of heavy metal water pollution from an integrated European perspective, i.e., to quantify through modelling a general model of water pollution reduction in the EU. The objectives of the study are mainly aimed at identifying effective solutions to reduce heavy metal water pollution and providing supranational decision-makers with public policy directions in the field. The research methods consist of the foundation of working hypotheses based on the study of the literature, the consolidation of official statistical databases in the field, econometric modelling and the conceptualisation of a general model and its testing and validation by statistical methods. The results of the analysis consist of the following marginal contributions: the identification of a general model for combating heavy metal pollution; the calculation of the degree of contribution of regional policies to the general model; and the identification of effective solutions to improve the combating of heavy metal water pollution in Europe. The main conclusion of the analysis shows that significant progress has been achieved at the EU level in the field of combating heavy metal water pollution. However, the level of disparity and poor policy coordination are real vulnerabilities for the EU.
Sex Differences in Frailty Factors and Their Capacity to Identify Frailty in Older Adults Living in Long-Term Nursing Homes
Authors: Arizaga-Iribarren Nagore , Irazusta Amaia , Mugica-Errazquin Itxaso , Virgala-García Janire , Amonarraiz Arantxa , Kortajarena Maider
Published: December 2022

Frailty is a phenomenon that precedes adverse health events in older people. However, there is currently no consensus for how to best measure frailty. Several studies report that women have a higher prevalence of frailty than men, but there is a gap in studies of the high rates of frailty in older people living in long-term nursing homes (LTNHs) stratified by sex. Therefore, we analyzed health parameters related to frailty and measured their capacity to identify frailty stratified by sex in older people living in LTNHs. According to the Fried Frailty Phenotype (FFP), anxiety increased the risk of frailty in women, while for men functionality protected against the risk of frailty. Regarding the Tilburg Frailty Indicator (TFI), functionality had a protective effect in men, while for women worse dynamic balance indicated a higher risk of frailty. The analyzed parameters had a similar capacity for detecting frailty measured by the TFI in both sexes, while the parameters differed in frailty measured by the FFP. Our study suggests that assessment of frailty in older adults should incorporate a broad definition of frailty that includes not only physical parameters but also psycho-affective aspects as measured by instruments such as the TFI.
Enabling Value Co-Creation in Healthcare through Blockchain Technology
Authors: Russo-Spena Tiziana , Mele Cristina , Cavacece Ylenia , Ebraico Sara , Dantas Carina , Roseiro Pedro , van Staalduinen Willeke
Published: December 2022

The COVID-19 pandemic highlighted the need to manage complex relations within the healthcare ecosystem. The role of new technologies in achieving this goal is a topic of current interest. Among them, blockchain technology is experiencing widespread application in the healthcare context. The present work investigates how this technology fosters value co-creation paths in the new digital healthcare ecosystems. To this end, a multiple case study has been conducted examining the development and application of blockchain by 32 healthcare tech companies. The results show blockchain technology adoption’s current and potential impacts on value co-creation regarding data and resource sharing, patient participation, and collaboration between professionals. Three main areas of activity emerge from the case studies where blockchain implementation brings significant benefits for value co-creation: improving service interaction, impacting actors’ engagement, and fostering ecosystem transparency.
Genome-Wide Analysis of Wheat GATA Transcription Factor Genes Reveals Their Molecular Evolutionary Characteristics and Involvement in Salt and Drought Tolerance
Authors: Du Xuan , Lu Yuxia , Sun Haocheng , Duan Wenjing , Hu Yingkao , Yan Yueming
Published: December 2022

GATA transcription factor genes participate in plant growth, development, morphogenesis, and stress response. In this study, we carried out a comprehensive genome-wide analysis of wheat GATA transcription factor genes to reveal their molecular evolutionary characteristics and involvement in salt and drought tolerance. In total, 79 TaGATA genes containing a conserved GATA domain were identified in the wheat genome, which were classified into four subfamilies. Collinear analysis indicated that fragment duplication plays an important role in the amplification of the wheat GATA gene family. Functional disproportionation analysis between subfamilies found that both type I and type II functional divergence simultaneously occurs in wheat GATA genes, which might result in functional differentiation of the TaGATA gene family. Transcriptional expression analysis showed that TaGATA genes generally have a high expression level in leaves and in response to drought and salt stresses. Overexpression of TaGATA62 and TaGATA73 genes significantly enhanced the drought and salt tolerance of yeast and Arabidopsis. Protein–protein docking indicated that TaGATAs can enhance drought and salt tolerance by interacting between the DNA-binding motif of GATA transcription factors and photomorphogenesis-related protein TaCOP9-5A. Our results provided a base for further understanding the molecular evolution and functional characterization of the plant GATA gene family in response to abiotic stresses.
Intrauterine Inflammation Leads to Select Sex- and Age-Specific Behavior and Molecular Differences in Mice
Authors: Cristancho Ana G. , Tulina Natalia , Brown Amy G. , Anton Lauren , Barila Guillermo , Elovitz Michal A.
Published: December 2022

Sex-specific differences in behavior have been observed in anxiety and learning in children exposed to prenatal inflammation; however, whether these behaviors manifest differently by age is unknown. This study assesses possible behavioral changes due to in utero inflammation as a function of age in neonatal, juvenile, and adult animals and presents potential molecular targets for observed differences. CD-1 timed pregnant dams were injected in utero with lipopolysaccharide (LPS, 50 μg/animal) or saline at embryonic day 15. No differences in stress responses were measured by neonatal ultrasonic vocalizations between LPS- and saline-exposed groups of either sex. By contrast, prenatal inflammation caused a male-specific increase in anxiety in mature but not juvenile animals. Juvenile LPS-exposed females had decreased movement in open field testing that was not present in adult animals. We additionally observed improved memory retrieval after in utero LPS in the juvenile animals of both sexes, which in males may be related to a perseverative phenotype. However, there was an impairment of long-term memory in only adult LPS-exposed females. Finally, gene expression analyses revealed that LPS induced sex-specific changes in genes involved in hippocampal neurogenesis. In conclusion, intrauterine inflammation has age- and sex-specific effects on anxiety and learning that may correlate to sex-specific disruption of gene expression associated with neurogenesis in the hippocampus.
Diet and Proteinuria: State of Art
Authors: Ria Paolo , De Pascalis Antonio , Zito Anna , Barbarini Silvia , Napoli Marcello , Gigante Antonietta , Sorice Gian Pio
Published: December 2022

Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.
Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man
Authors: Rodríguez-Daza María Carolina , de Vos Willem M.
Published: December 2022

Akkermansia muciniphila is a mucosal symbiont considered a gut microbial marker in healthy individuals, as its relative abundance is significantly reduced in subjects with gut inflammation and metabolic disturbances. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. However, mechanistic insight into how polyphenols stimulate A. muciniphila or its activity is limited. This review focuses on dietary interventions in rodents and humans and in vitro studies using different phenolic classes. We provide critical insights with respect to potential mechanisms explaining the effects of polyphenols affecting A. muciniphila. Anthocyanins, flavan-3-ols, flavonols, flavanones, stilbenes, and phenolic acids are shown to increase relative A. muciniphila levels in vivo, whereas lignans exert the opposite effect. Clinical trials show consistent findings, and high intervariability relying on the gut microbiota composition at the baseline and the presence of multiple polyphenol degraders appear to be cardinal determinants in inducing A. muciniphila and associated benefits by polyphenol intake. Polyphenols signal to the AhR receptor and impact the relative abundance of A. muciniphila in a direct and indirect fashion, resulting in the restoration of intestinal epithelial integrity and homeostatic crosstalk with the gut microbiota by affecting IL-22 production. Moreover, recent evidence suggests that A. muciniphila participates in the initial hydrolysis of some polyphenols but does not participate in their complete metabolism. In conclusion, the consumption of polyphenol-rich foods targeting A. muciniphila as a pivotal intermediary represents a promising precision nutritional therapy to prevent and attenuate metabolic and inflammatory diseases.
Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P-Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects
Authors: Albalawi Fawzia F. , El-Nassag Mohammed A. A. , El-Eisawy Raafat A. , Mohamed Mahmoud Basseem I. , Fouda Ahmed M. , Afifi Tarek H. , Elhenawy Ahmed A. , Mora Ahmed , El-Agrody Ahmed M. , El-Mawgoud Heba K. A.
Published: December 2022

β-Enaminonitriles bearing 9-hydroxy-1H-benzo[f]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P-gp inhibitor. Moreover, the halogenated substituents, 2,4-F2, 2,3-Cl2, 2,5-Cl2 and 3,4-Cl2; have good potency against P-gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P-pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria
Authors: Solares Isabel , Jericó Daniel , Córdoba Karol M. , Morales-Conejo Montserrat , Ena Javier , Enríquez de Salamanca Rafael , Fontanellas Antonio
Published: December 2022

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks associated with high production, accumulation and urinary excretion of heme precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). The estimated clinical penetrance for AIP is extremely low (<1%), therefore it is likely that other factors may play an important role in the predisposition to developing attacks. Fasting is a known triggering factor. Given the increased prevalence of insulin resistance in patients and the large urinary loss of succinyl-CoA to produce ALA and PBG, we explore the impact of reduced availability of energy metabolites in the severity of AIP pathophysiology. Classic studies found clinical improvement in patients affected by AIP associated with the administration of glucose and concomitant insulin secretion, or after hyperinsulinemia associated with diabetes. Molecular studies have confirmed that glucose and insulin administration induces a repressive effect on hepatic ALA Synthase, the first and regulatory step of the heme pathway. More recently, the insulin-mimicking α-lipoic acid has been shown to improve glucose metabolism and mitochondrial dysfunction in a hepatocyte cell line transfected with interfering RNA targeting PBGD. In AIP mice, preventive treatment with an experimental fusion protein of insulin and apolipoprotein A-I improved the disease by promoting fat mobilization in adipose tissue, increasing the metabolite bioavailability for the TCA cycle and inducing mitochondrial biogenesis in the liver. In this review, we analyze the possible mechanisms underlying abnormal hepatocellular carbohydrate homeostasis in AIP.
Influence of Drying Temperature and Harvesting Season on Phenolic Content and Antioxidant and Antiproliferative Activities of Olive (Olea europaea) Leaf Extracts
Authors: Losada-Echeberría María , Naranjo Gustavo , Malouche Dhafer , Taamalli Amani , Barrajón-Catalán Enrique , Micol Vicente
Published: December 2022

Interest in plant compounds has increased, given recent evidence regarding their role in human health due to their pleiotropic effects. For example, plant bioactive compounds present in food products, including polyphenols, are associated with preventive effects in various diseases, such as cancer or inflammation. Breast and colorectal cancers are among the most commonly diagnosed cancers globally. Although appreciable advances have been made in treatments, new therapeutic approaches are still needed. Thus, in this study, up to 28 olive leaf extracts were obtained during different seasons and using different drying temperatures. The influence of these conditions on total polyphenolic content (measured using Folin–Ciocalteu assays), antioxidant activity (using Trolox Equivalent Antioxidant Capacity and Ferric Reducing Ability of Plasma assays) and antiproliferative capacity (using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assays) was tested in breast and colorectal cancer cells. Increased phenolic composition and antioxidant and antiproliferative capacity are noted in the extracts obtained from leaves harvested in autumn, followed by summer, spring and winter. Regarding drying conditions, although there is not a general trend, conditions using the highest temperatures lead to the optimal phenolic content and antioxidant and antiproliferative activities in most cases. These results confirm previously published studies and provide evidence in support of the influence of both harvesting and drying conditions on the biological activity of olive leaf extracts.
Structure-Based Function and Regulation of NCX Variants: Updates and Challenges
Authors: Khananshvili Daniel
Published: December 2022

The plasma-membrane homeostasis Na+/Ca2+ exchangers (NCXs) mediate Ca2+ extrusion/entry to dynamically shape Ca2+ signaling/in biological systems ranging from bacteria to humans. The NCX gene orthologs, isoforms, and their splice variants are expressed in a tissue-specific manner and exhibit nearly 104-fold differences in the transport rates and regulatory specificities to match the cell-specific requirements. Selective pharmacological targeting of NCX variants could benefit many clinical applications, although this intervention remains challenging, mainly because a full-size structure of eukaryotic NCX is unavailable. The crystal structure of the archaeal NCX_Mj, in conjunction with biophysical, computational, and functional analyses, provided a breakthrough in resolving the ion transport mechanisms. However, NCX_Mj (whose size is nearly three times smaller than that of mammalian NCXs) cannot serve as a structure-dynamic model for imitating high transport rates and regulatory modules possessed by eukaryotic NCXs. The crystal structures of isolated regulatory domains (obtained from eukaryotic NCXs) and their biophysical analyses by SAXS, NMR, FRET, and HDX-MS approaches revealed structure-based variances of regulatory modules. Despite these achievements, it remains unclear how multi-domain interactions can decode and integrate diverse allosteric signals, thereby yielding distinct regulatory outcomes in a given ortholog/isoform/splice variant. This article summarizes the relevant issues from the perspective of future developments.
CT and MRI Imaging of Theranostic Bimodal Fe3O4@Au NanoParticles in Tumor Bearing Mice
Authors: Lipengolts Alexey A. , Finogenova Yulia A. , Skribitsky Vsevolod A. , Shpakova Kristina E. , Anaki Adi , Motiei Menachem , Semkina Alevtina S. , Abakumov Maxim A. , Smirnova Anna V. , Grigorieva Elena Y. , Popovtzer Rachela
Published: December 2022

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe3O4 core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe3O4@Au theranostic nanoparticles. Core/shell Fe3O4@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe3O4@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe3O4@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.
AML1-ETO-Related Fusion Circular RNAs Contribute to the Proliferation of Leukemia Cells
Authors: Wang Ying , Liu Yu , Xu Yingxi , Xing Haiyan , Tian Zheng , Tang Kejing , Rao Qing , Wang Min , Wang Jianxiang
Published: December 2022

The AML1-ETO (RUNX1-RUNX1T1) fusion gene created by the chromosome translocation t(8;21) (q21;q22) is one of the essential contributors to leukemogenesis. Only a few studies in the literature have focused on fusion gene-derived circular RNAs (f-circRNAs). Here, we report several AML1-ETO-related fusion circular RNAs (F-CircAEs) in AML1-ETO-positive cell lines and primary patient blasts. Functional studies demonstrate that the over-expression of F-CircAE in NIH3T3 cells promotes cell proliferation in vitro and in vivo. F-CircAE expression enhances the colony formation ability of c-Kit+ hematopoietic stem and progenitor cells (HSPCs). Meanwhile, the knockdown of endogenous F-CircAEs can inhibit the proliferation and colony formation ability of AML1-ETO-positive Kasumi-1 cells. Intriguingly, bioinformatic analysis revealed that the glycolysis pathway is down-regulated in F-CircAE-knockdown Kasumi-1 cells and up-regulated in F-CircAE over-expressed NIH3T3 cells. Further studies show that F-CircAE binds to the glycolytic protein ENO-1, up-regulates the expression level of glycolytic enzymes, and enhances lactate production. In summary, our study demonstrates that F-CircAE may exert biological activities on the growth of AML1-ETO leukemia cells by regulating the glycolysis pathway. Determining the role of F-CircAEs in AML1-ETO leukemia can lead to great strides in understanding its pathogenesis, thus providing new diagnostic markers and therapeutic targets.
A Review of Oil–Solid Separation and Oil–Water Separation in Unconventional Heavy Oil Production Process
Authors: Xia Xiao , Ma Jun , Geng Shuo , Liu Fei , Yao Mengqin
Published: December 2022

Unconventional heavy oil ores (UHO) have been considered an important part of petroleum resources and an alternative source of chemicals and energy supply. Due to the participation of water and extractants, oil–solid separation (OSS) and oil–water separation (OWS) processes are inevitable in the industrial separation processes of UHO. Therefore, this critical review systematically reviews the basic theories of OSS and OWS, including solid wettability, contact angle, oil–solid interactions, structural characteristics of natural surfactants and interface characteristics of interfacially active asphaltene film. With the basic theories in mind, the corresponding OSS and OWS mechanisms are discussed. Finally, the present challenges and future research considerations are touched on to provide insights and theoretical fundamentals for OSS and OWS. Additionally, this critical review might even be useful for the provision of a framework of research prospects to guide future research directions in laboratories and industries that focus on the OSS and OWS processes in this important heavy oil production field.
Higher Circulating Levels of Neutrophils and Basophils Are Linked to Myopic Retinopathy
Authors: Qi Jinyan , Pan Wei , Peng Ting , Zeng Ling , Li Xiaoning , Chen Zhongping , Yang Zhikuan , Xu Heping
Published: December 2022

This retrospective study investigated circulating immune cell alteration in patients with myopic retinopathy. Blood test results and demographic and ocular information of 392 myopic patients and 129 emmetropia controls who attended Changsha Aier Eye Hospital from May 2017 to April 2022 were used in this study. Compared with emmetropia, the percentages of neutrophils and basophils and neutrophil/lymphocyte ratio were significantly higher in myopic patients, whereas the percentages of monocytes and lymphocytes and the counts of lymphocytes and eosinophils were significantly lower in myopic patients. After adjusting for age and hypertension/diabetes, the difference remained. Interestingly, the platelet counts were significantly lower in myopic patients after the adjustments. Further subgroup analysis using multivariable linear regression showed that higher levels of neutrophils, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio, lower levels of monocytes, eosinophils, lymphocytes, and platelets, were related to myopic peripheral retinal degeneration (mPRD) and posterior staphyloma (PS). A higher level of basophils was linked to myopic choroidal neovascularization (mCNV). Our results suggest that higher levels of circulating neutrophils and neutrophil/lymphocyte ratio, lower monocytes, eosinophils, lymphocytes, and platelets are related to mild myopic retinopathy. A higher level of circulating basophils is related to the severe form of myopic retinopathy, such as mCNV.
The Normobaric Oxygen Paradox—Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues
Authors: Salvagno Michele , Coppalini Giacomo , Taccone Fabio Silvio , Strapazzon Giacomo , Mrakic-Sposta Simona , Rocco Monica , Khalife Maher , Balestra Costantino
Published: December 2022

Hypoxia, even at non-lethal levels, is one of the most stressful events for all aerobic organisms as it significantly affects a wide spectrum of physiological functions and energy production. Aerobic organisms activate countless molecular responses directed to respond at cellular, tissue, organ, and whole-body levels to cope with oxygen shortage allowing survival, including enhanced neo-angiogenesis and systemic oxygen delivery. The benefits of hypoxia may be evoked without its detrimental consequences by exploiting the so-called normobaric oxygen paradox. The intermittent shift between hyperoxic-normoxic exposure, in addition to being safe and feasible, has been shown to enhance erythropoietin production and raise hemoglobin levels with numerous different potential applications in many fields of therapy as a new strategy for surgical preconditioning aimed at frail patients and prevention of postoperative anemia. This narrative review summarizes the physiological processes behind the proposed normobaric oxygen paradox, focusing on the latest scientific evidence and the potential applications for this strategy. Future possibilities for hyperoxic-normoxic exposure therapy include implementation as a synergistic strategy to improve a patient’s pre-surgical condition, a stimulating treatment in critically ill patients, preconditioning of athletes during physical preparation, and, in combination with surgery and conventional chemotherapy, to improve patients’ outcomes and quality of life.
Vitamin D in Neurological Diseases
Authors: Plantone Domenico , Primiano Guido , Manco Carlo , Locci Sara , Servidei Serenella , De Stefano Nicola
Published: December 2022

Vitamin D may have multiple effects on the nervous system and its deficiency can represent a possible risk factor for the development of many neurological diseases. Recent studies are also trying to clarify the different effects of vitamin D supplementation over the course of progressive neurological diseases. In this narrative review, we summarise vitamin D chemistry, metabolism, mechanisms of action, and the recommended daily intake. The role of vitamin D on gene transcription and the immune response is also reviewed. Finally, we discuss the scientific evidence that links low 25-hydroxyvitamin D concentrations to the onset and progression of severe neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, migraine, diabetic neuropathy and amyotrophic lateral sclerosis. Completed and ongoing clinical trials on vitamin D supplementation in neurological diseases are listed.