bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferential Binding of Polyphenols in Blackcurrant Extracts with Milk Proteins and the Effects on the Bioaccessibility and Antioxidant Activity of Polyphenols
Authors: Mao Ting , Akshit FNU , Matiwalage Iresha , Sasidharan Subha , Alvarez Caren Meyn , Wescombe Philip , Mohan Maneesha S.
Published: February 2024

Milk proteins are well-known delivery agents; however, there is no clear understanding of the competitive interactions of milk proteins with polyphenols in mixed complex systems. Here, we investigate the preferential competitive interactions of different polyphenols present in blackcurrant extract with milk proteins by quantifying the protein-bound polyphenols and comparing the factors affecting these interactions. In addition, bioaccessibility and antioxidant activity were studied after in vitro gastric digestion. Our results indicated that polyphenols from blackcurrant extracts were preferentially bound to caseins more than whey proteins, with noncovalent interactions causing secondary structural changes in the protein. The hydrophobicity and the charge of the polyphenols were negatively and positively related to the number of polyphenols bound to casein and whey proteins, respectively. Moreover, the bioaccessibility and antioxidant activity of polyphenols were enhanced in the presence of milk proteins in milk-based blackcurrant samples when compared to polyphenol and protein-alone samples in the in vitro gastric phase. These findings underscore the critical role of milk proteins in encapsulating or delivering polyphenols. This will pave the way for boosting the bioavailability of polyphenols by complexing them with milk proteins and formulating functional dairy foods, integrating the beneficial effects of these compounds.
Review of the Fractional Black-Scholes Equations and Their Solution Techniques
Authors: Zhang Hongmei , Zhang Mengchen , Liu Fawang , Shen Ming
Published: February 2024

The pioneering work in finance by Black, Scholes and Merton during the 1970s led to the emergence of the Black-Scholes (B-S) equation, which offers a concise and transparent formula for determining the theoretical price of an option. The establishment of the B-S equation, however, relies on a set of rigorous assumptions that give rise to several limitations. The non-local property of the fractional derivative (FD) and the identification of fractal characteristics in financial markets have paved the way for the introduction and rapid development of fractional calculus in finance. In comparison to the classical B-S equation, the fractional B-S equations (FBSEs) offer a more flexible representation of market behavior by incorporating long-range dependence, heavy-tailed and leptokurtic distributions, as well as multifractality. This enables better modeling of extreme events and complex market phenomena, The fractional B-S equations can more accurately depict the price fluctuations in actual financial markets, thereby providing a more reliable basis for derivative pricing and risk management. This paper aims to offer a comprehensive review of various FBSEs for pricing European options, including associated solution techniques. It contributes to a deeper understanding of financial model development and its practical implications, thereby assisting researchers in making informed decisions about the most suitable approach for their needs.
Space–Time Variations in the Long-Range Dependence of Sea Surface Chlorophyll in the East China Sea and the South China Sea
Authors: He Junyu , Li Ming
Published: February 2024

Gaining insights into the space–time variations in the long-range dependence of sea surface chlorophyll is crucial for the early detection of environmental issues in oceans. To this end, 12 locations were selected along the Yangtze River and Pearl River estuaries, varying in distances from the Chinese coastline. Daily satellite-observed sea surface chlorophyll concentration data at these 12 locations were collected from the Copernicus Marine Service website, spanning from December 1997 to November 2023. The main objective of the current study is to introduce a multi-fractional generalized Cauchy model for calculating the values of Hurst exponents and quantitatively assessing the long-range dependence strength of sea surface chlorophyll at different spatial locations and time instants during the study period. Furthermore, ANOVA was utilized to detect the differences of calculated Hurst exponent values among the locations during various months and seasons. From a spatial perspective, the findings reveal a significantly stronger long-range dependence of sea surface chlorophyll in offshore regions compared to nearshore areas, with Hurst exponent values > 0.5 versus <0.5. It is noteworthy that the values of Hurst exponents at each location exhibit significant differences during various seasons, from a temporal perspective. Specifically, the long-range dependence of sea surface chlorophyll in summer in the nearshore region is weaker than in other seasons, whereas that in the offshore region is stronger than in other seasons. The study concludes that long-range dependence is inversely related to the distance from the coastline, and anthropogenic activity plays a dominant role in shaping the long-range dependence of sea surface chlorophyll in the coastal regions of China.
Methodology for Monitoring Border Crossing Delays with Connected Vehicle Data: United States and Mexico Land Crossings Case Study
Authors: Sakhare Rahul Suryakant , Desai Jairaj , Saldivar-Carranza Enrique D. , Bullock Darcy M.
Published: February 2024

International trade is a critical part of the United States economy. Land border crossings between the United States and Mexico accounts for a large proportion of the USD 779 billion in trade between these two countries. Monitoring and managing the operations of these land border crossings is critical for ensuring efficient trade and providing appropriate security. This paper examines the opportunity to use connected vehicle data to monitor the travel time delay of passenger vehicles crossing the border for system level assessment across 26 border crossing locations over an analysis period of 25 days in August 2020. A sample size of 51,341 trips from the US to Mexico and 41,708 trips from Mexico to the US were used in this study. Furthermore, 97% trips to the US and 76% trips to Mexico experienced delays. The average delay was 34 min for trips to the US compared to only 2 min for trips to Mexico. In terms of the predictability of border crossing times, there was also substantial variation by direction. The interquartile range of vehicle delay from the US to Mexico was 2 min, while the interquartile range of delay for vehicles travelling from Mexico to the US was 46 min. Border crossings were also ranked using four performance metrics—trip counts, median delay, delayed trip counts and total delays in vehicle hours. Methods for summarizing delay trends by time of the day and day of the week to identify time windows of interest are also presented. Land border crossing operations have a significant influence on security and economic efficiency. We believe the techniques presented in this paper provide a scalable methodology for providing near real-time factual data on border crossing delays that provide important information for land border transport-managing stakeholders to make informed management decisions that balance security and economic efficiency.
Shared E-Scooter Practices in Birmingham, Alabama: Analyzing Usage, Patterns, and Determinants
Authors: Hasan Mithila , Sisiopiku Virginia P.
Published: February 2024

Shared micromobility has gained significant attention in the field of transportation engineering in recent years as an environmentally friendly, convenient, and easily accessible transportation mode. Like other medium-sized cities, Birmingham, Alabama implemented a shared micromobility pilot program in 2021 that captured the attention of local travelers. This study examined shared e-scooter usage and associated travel patterns in Birmingham using 2021–2022 field data. From these data, ArcGIS maps were used to showcase trip origins and destinations. To gain a further understanding of e-scooter travel patterns in the study area, zip code and block group densities were calculated. Additionally, a negative binomial regression model was constructed to identify determinants of shared e-scooter trips. The analysis results showed that the usage of shared e-scooters was the highest during the nighttime (9109 trips between 9 p.m. to 10 p.m.), on weekends (20,077 trips on Saturday), and in the fall season (a total of 29,024 trips). Furthermore, the research findings indicated that shared e-scooters experienced their highest utilization rates in areas with a higher proportion of educated and higher-income individuals. These findings suggest that travelers’ mode choice related to the use of micromobility modes is influenced by environmental and demographic factors. Overall, this case study offers valuable contributions to the understanding of the role of shared e-scooters in Birmingham’s transportation landscape and can guide transportation authorities in other medium-sized cities in their efforts to plan for micromobility options.
The Effects of Soft-Tissue Techniques and Exercise in the Treatment of Patellar Tendinopathy—Systematic Review and Meta-Analysis
Authors: Ragone Federico , Pérez-Guillén Silvia , Carrasco-Uribarren Andoni , Cabanillas-Barea Sara , Ceballos-Laita Luis , Rodríguez-Rubio Pere Ramón , Cabanas-Valdés Rosa
Published: February 2024

Background: Patellar tendinopathy is a degenerative clinical disorder that causes load-related pain in the lower pole of the patella or patellar tendon. It predominantly affects young male athletes engaged in sports involving repetitive tendon loading, particularly explosive jumping. The combination of manual techniques with therapeutic exercise is hypothesized to provide greater benefits than exercise alone. Objective: The aim of this study is to analyze the scientific evidence regarding the effects of soft-tissue techniques combined with therapeutic exercise versus therapeutic exercise alone on pain intensity and function in individuals with patellar tendinopathy. Methods: A systematic review with meta-analysis was conducted following the PRISMA guidelines. PubMed, Lilacs, IBECS, CENTRAL, WOS, SciELO, Academic Search, CINAHL, SportDiscus, PEDro, and Google Scholar databases were consulted. Randomized controlled trials and quasi-randomized trials focusing on the effects of soft-tissue techniques combined with therapeutic exercise (experimental group) versus therapeutic exercise alone (control group) on pain and function in individuals aged 16 years and older with patellar tendinopathy were selected. The Cochrane tool for risk-of-bias assessment and the PEDro scale for methodological quality were used. Results and Discussion: A total of six studies (n = 309; age range = 16–40 years), considered to have a low risk of bias and moderate-to-high methodological quality, were included. The results showed improvements in function in the experimental group (mean of 60% on the Visa-P scale) and pain in the experimental group (mean decrease of 2 points in the VAS scale). There were improvements in 50% of the studies when comparing variables between the experimental and control groups. Conclusions: The combination of manual techniques, such as dry needling, percutaneous electrolysis, transverse friction massage, and stretching, along with a squat on a 25° inclined plane, appears to be effective in the treatment of patellar tendinopathy. Static stretching of the quadriceps before and after the squat five times per week, along with dry needling or percutaneous electrolysis sessions twice a week for 8 weeks, is recommended. However, future studies analyzing groups with passive techniques versus therapeutic exercise are needed to standardize the treatment and establish the optimal dose.
Negative Associations between Minority Stressors and Self-Reported Health Status among Sexual Minority Adults Living in Colombia
Authors: Roldán Paola , Matijczak Angela , Goffnett Jacob
Published: February 2024

Colombia has extensive laws prohibiting discrimination against sexual minority people. However, violence and discrimination toward sexual minorities are still frequent. While a growing body of research shows that sexual minority people experience elevated rates of discrimination and domestic abuse globally, little research has been conducted on these issues affecting sexual minorities in Colombia specifically. Using minority stress theory as a conceptual framework, this paper aims to fill this gap by examining the prevalence of experiencing intimate partner violence (IPV) and witnessed discrimination and the relationship of these stressors to self-reported health among a national sample of sexual minority Colombians. We found that bisexual individuals experienced higher rates of physical and sexual IPV, compared to lesbian and gay individuals. Additionally, sexual minority Colombians who experienced IPV and witnessed discrimination were more likely to report having poorer health, compared to those who had not. We discuss the implications of our findings for future research and clinicians working with sexual minority clients.
The Mental Wellbeing of Child and Adolescent Mental Health Service (CAMHS) Workers in England: A Cross-Sectional Descriptive Study Reporting Levels of Burnout, Wellbeing and Job Satisfaction
Authors: Mareva Silvana , Chapman Beth , Hardwick Rebecca , Hewlett Charlotte , Mitchell Siobhan , Sanders Amy , Hayes Rachel
Published: February 2024

In the UK, there has been a notable increase in referrals to specialist children’s mental health services. This, coupled with shortages of qualified staff, has raised concerns about the escalating occupational stress experienced by staff in this sector. In this brief report, we present cross-sectional quantitative data from 97 staff members working in one Child and Adolescent Mental Health Service (CAMHS) in the UK during spring 2023, reporting on their wellbeing, job satisfaction, and burnout. Our findings reveal that over a third of CAMHS staff experienced moderate or high levels of work-related burnout; 39% reported moderate or high levels of personal burnout, but levels of client-related burnout were much lower (13%). Both work- and client-related burnout showed a robust negative relationship with job satisfaction, with higher burnout predicting lower levels of job satisfaction. Only a small proportion of respondents reported high levels of wellbeing, with about a quarter experiencing levels of wellbeing that can be considered indicative of mild or clinical depressive symptoms. Whilst these results are from a small sample in one area of the UK, they present an important snapshot of CAMHS staff wellbeing and are discussed in the context of similar trends reported in the wider NHS sector.
Impact of the Italian Healthcare Outcomes Program (PNE) on the Care Quality of the Poorest Performing Hospitals
Authors: Fiore Matteo , Bianconi Alessandro , Acuti Martellucci Cecilia , Rosso Annalisa , Zauli Enrico , Flacco Maria Elena , Manzoli Lamberto
Published: February 2024

One of the main aims of the Italian National Healthcare Outcomes Program (Programma Nazionale Esiti, PNE) is the identification of the hospitals with the lowest performance, leading them to improve their quality. In order to evaluate PNE impact for a subset of outcome indicators, we evaluated whether the performance of the hospitals with the lowest scores in 2016 had significantly improved after five years. The eight indicators measured the risk-adjusted likelihood of the death of each patient (adjusted relative risk—RR) 30 days after the admission for acute myocardial infarction, congestive heart failure, stroke, chronic obstructive pulmonary disease, chronic kidney disease, femur fracture or lung and colon cancer. In 2016, the PNE identified 288 hospitals with a very low performance in at least one of the selected indicators. Overall, 51.0% (n = 147) of these hospitals showed some degree of improvement in 2021, and 27.4% of them improved so much that the death risk of their patients fell below the national mean value. In 34.7% of the hospitals, however, the patients still carried a mean risk of death >30% higher than the average Italian patient with the same disease. Only 38.5% of the hospitals in Southern Italy improved the scores of the selected indicators, versus 68.0% in Northern and Central Italy. Multivariate analyses, adjusting for the baseline performance in 2016, confirmed univariate results and showed a significantly lower likelihood of improvement with increasing hospital volume. Despite the overall methodological validity of the PNE system, current Italian policies and actions aimed at translating hospital quality scores into effective organizational changes need to be reinforced with a special focus on larger southern regions.
Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study
Authors: Morimoto Masaya , Yokoya Yuma , Yoshida Kikuaki , Kosako Hideki , Hori Yoshikazu , Mushino Toshiki , Tamura Shinobu , Ito Reiko , Koyamada Ryosuke , Yamashita Takuya , Mori Shinichiro , Mori Nobuyoshi , Ohde Sachiko
Published: February 2024

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for a positive hepatitis panel, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777–0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.
Using Concepts of Photovoice to Engage in Discussions Related to Burnout and Wellbeing
Authors: Macy Gretchen , Harper Whitney , Murphy April , Link Kim , Griffiths Austin , Win Shwe , East Ashley
Published: February 2024

The purpose of this study was to identify essential skills and abilities for mitigating job-related stressors and preventing burnout while also establishing connections between students and community health workers to provide students with a deeper comprehension of the challenges inherent to their future professions. Ten community health workers were interviewed and asked to present photographs that explored sources of burnout and promotions of well-being. The photographs along with quotes were displayed in a gallery style exhibit for students to view and talk with the community health workers and complete a survey. Using thematic analysis, the interviews resulted in four common factors that contribute to burnout: (1) workload demands, (2) unrealistic exceptions, (3) amount of time dedicated to care, and (4) lack of work–life balance. The themes that emerged from student responses were (1) learning self-care practices, (2) gaining insight into the need for self-care, (3) a sense of connection, and (4) exposure to different healthcare careers. This study demonstrates the importance of connecting students with community health workers. It increases understanding of the demands of their future professions as well as resources and engagement opportunities available to them as a part of their respective professional community.
Special Issue with Research Topics on “Recent Analysis and Applications of Mass Spectra on Biochemistry”
Authors: Ivanova Bojidarka
Published: February 2024

Analytical mass spectrometry applies irreplaceable mass spectrometric (MS) methods to analytical chemistry and chemical analysis, among other areas of analytical science [...]
Mesophiles vs. Thermophiles: Untangling the Hot Mess of Intrinsically Disordered Proteins and Growth Temperature of Bacteria
Authors: Kruglikov Alibek , Xia Xuhua
Published: February 2024

The dynamic structures and varying functions of intrinsically disordered proteins (IDPs) have made them fascinating subjects in molecular biology. Investigating IDP abundance in different bacterial species is crucial for understanding adaptive strategies in diverse environments. Notably, thermophilic bacteria have lower IDP abundance than mesophiles, and a negative correlation with optimal growth temperature (OGT) has been observed. However, the factors driving these trends are yet to be fully understood. We examined the types of IDPs present in both mesophiles and thermophiles alongside those unique to just mesophiles. The shared group of IDPs exhibits similar disorder levels in the two groups of species, suggesting that certain IDPs unique to mesophiles may contribute to the observed decrease in IDP abundance as OGT increases. Subsequently, we used quasi-independent contrasts to explore the relationship between OGT and IDP abundance evolution. Interestingly, we found no significant relationship between OGT and IDP abundance contrasts, suggesting that the evolution of lower IDP abundance in thermophiles may not be solely linked to OGT. This study provides a foundation for future research into the intricate relationship between IDP evolution and environmental adaptation. Our findings support further research on the adaptive significance of intrinsic disorder in bacterial species.
VSpipe-GUI, an Interactive Graphical User Interface for Virtual Screening and Hit Selection
Authors: Hussain Rashid , Hackett Andrew Scott , Álvarez-Carretero Sandra , Tabernero Lydia
Published: February 2024

Virtual screening of large chemical libraries is essential to support computer-aided drug development, providing a rapid and low-cost approach for further experimental validation. However, existing computational packages are often for specialised users or platform limited. Previously, we developed VSpipe, an open-source semi-automated pipeline for structure-based virtual screening. We have now improved and expanded the initial command-line version into an interactive graphical user interface: VSpipe-GUI, a cross-platform open-source Python toolkit functional in various operating systems (e.g., Linux distributions, Windows, and Mac OS X). The new implementation is more user-friendly and accessible, and considerably faster than the previous version when AutoDock Vina is used for docking. Importantly, we have introduced a new compound selection module (i.e., spatial filtering) that allows filtering of docked compounds based on specified features at the target binding site. We have tested the new VSpipe-GUI on the Hepatitis C Virus NS3 (HCV NS3) protease as the target protein. The pocket-based and interaction-based modes of the spatial filtering module showed efficient and specific selection of ligands from the virtual screening that interact with the HCV NS3 catalytic serine 139.
Genome-Wide Identification and Expression Profile Analysis of Sugars Will Eventually Be Exported Transporter (SWEET) Genes in Zantedeschia elliottiana and Their Responsiveness to Pectobacterium carotovora subspecies Carotovora (Pcc) Infection
Authors: Li Ziwei , Guo Yanbing , Jin Shoulin , Wu Hongzhi
Published: February 2024

SWEET, sugars will eventually be exported transporter, is a novel class of sugar transporter proteins that can transport sugars across membranes down a concentration gradient. It plays a key role in plant photosynthetic assimilates, phloem loading, nectar secretion from nectar glands, seed grouting, pollen development, pathogen interactions, and adversity regulation, and has received widespread attention in recent years. To date, systematic analysis of the SWEET family in Zantedeschia has not been documented, although the genome has been reported in Zantedeschia elliottiana. In this study, 19 ZeSWEET genes were genome-wide identified in Z. elliottiana, and unevenly located in 10 chromosomes. They were further clustered into four clades by a phylogenetic tree, and almost every clade has its own unique motifs. Synthetic analysis confirmed two pairs of segmental duplication events of ZeSWEET genes. Heatmaps of tissue-specific and Pectobacterium carotovora subsp. Carotovora (Pcc) infection showed that ZeSWEET genes had different expression patterns, so SWEETs may play widely varying roles in development and stress tolerance in Zantedeschia. Moreover, quantitative reverse transcription-PCR (qRT-PCR) analysis revealed that some of the ZeSWEETs responded to Pcc infection, among which eight genes were significantly upregulated and six genes were significantly downregulated, revealing their potential functions in response to Pcc infection. The promoter sequences of ZeSWEETs contained 51 different types of the 1380 cis-regulatory elements, and each ZeSWEET gene contained at least two phytohormone responsive elements and one stress response element. In addition, a subcellular localization study indicated that ZeSWEET07 and ZeSWEET18 were found to be localized to the plasma membrane. These findings provide insights into the characteristics of SWEET genes and contribute to future studies on the functional characteristics of ZeSWEET genes, and then improve Pcc infection tolerance in Zantedeschia through molecular breeding.
A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position
Authors: Klabenkova Kristina V. , Zhdanova Polina V. , Burakova Ekaterina A. , Bizyaev Sergei N. , Fokina Alesya A. , Stetsenko Dmitry A.
Published: February 2024

Staudinger reaction on the solid phase between an electronodeficit organic azide, such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for the chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide, either with a free carboxy group or in the form of an activated ester such as pentafluorophenyl, 4-nitrophenyl, or pentafluorobenzyl, was used to introduce a carboxylic acid function to the terminal or internal internucleotidic phosphate of an oligonucleotide via the Staudinger reaction. A subsequent treatment with excess primary alkyl amine followed by the usual work-up, after prior activation with a suitable peptide coupling agent such as a uronium salt/1-hydroxybenzotriazole in the case of a free carboxyl, afforded amide-linked oligonucleotide conjugates in good yields including multiple conjugations of up to the exhaustive modification at each phosphate position for a weakly activated pentafluorobenzyl ester, whereas more strongly activated and, thus, more reactive aryl esters provided only single conjugations at the 5′-end. The conjugates synthesized include those with di- and polyamines that introduce a positively charged side chain to potentially assist the intracellular delivery of the oligonucleotide.
Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges
Authors: Watanabe Hirohisa , Dijkstra Johannes M. , Nagatsu Toshiharu
Published: February 2024

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The reasons why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans are still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite the fact that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.
Unveiling Polysomal Long Non-Coding RNA Expression on the First Day of Adipogenesis and Osteogenesis in Human Adipose-Derived Stem Cells
Authors: Bonilauri Bernardo , Ribeiro Annanda Lyra , Spangenberg Lucía , Dallagiovanna Bruno
Published: February 2024

Understanding the intricate molecular mechanisms governing the fate of human adipose-derived stem cells (hASCs) is essential for elucidating the delicate balance between adipogenic and osteogenic differentiation in both healthy and pathological conditions. Long non-coding RNAs (lncRNAs) have emerged as key regulators involved in lineage commitment and differentiation of stem cells, operating at various levels of gene regulation, including transcriptional, post-transcriptional, and post-translational processes. To gain deeper insights into the role of lncRNAs’ in hASCs’ differentiation, we conducted a comprehensive analysis of the lncRNA transcriptome (RNA-seq) and translatome (polysomal-RNA-seq) during a 24 h period of adipogenesis and osteogenesis. Our findings revealed distinct expression patterns between the transcriptome and translatome during both differentiation processes, highlighting 90 lncRNAs that are exclusively regulated in the polysomal fraction. These findings underscore the significance of investigating lncRNAs associated with ribosomes, considering their unique expression patterns and potential mechanisms of action, such as translational regulation and potential coding capacity for microproteins. Additionally, we identified specific lncRNA gene expression programs associated with adipogenesis and osteogenesis during the early stages of cell differentiation. By shedding light on the expression and potential functions of these polysome-associated lncRNAs, we aim to deepen our understanding of their involvement in the regulation of adipogenic and osteogenic differentiation, ultimately paving the way for novel therapeutic strategies and insights into regenerative medicine.
The IGF–PAPP-A–Stanniocalcin Axis in Serum and Ascites Associates with Prognosis in Patients with Ovarian Cancer
Authors: Hjortebjerg Rikke , Høgdall Claus , Hansen Kristian Horsman , Høgdall Estrid , Frystyk Jan
Published: February 2024

Pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2 modulate insulin-like growth factor (IGF) action and are inhibited by the stanniocalcins (STC1 and STC2). We previously demonstrated increased PAPP-A and IGF activity in ascites from women with ovarian carcinomas. In this prospective, longitudinal study of 107 women with ovarian cancer and ascites accumulation, we determined corresponding serum and ascites levels of IGF-1, IGF-2, PAPP-A, PAPP-A2, STC1, and STC2 and assessed their relationship with mortality. As compared to serum, we found highly increased ascites levels of PAPP-A (51-fold) and PAPP-A2 (4-fold). Elevated levels were also observed for IGF-1 (12%), STC1 (90%) and STC2 (68%). In contrast, IGF-2 was reduced by 29% in ascites. Patients were followed for a median of 38.4 months (range: 45 days to 8.9 years), during which 73 patients (68.2%) died. Overall survival was longer for patients with high serum IGF-1 (hazard ratio (HR) per doubling in protein concentration: 0.60, 95% CI: 0.40–0.90). However, patients with high ascites levels of IGF-1 showed a poorer prognosis (HR: 2.00 (1.26–3.27)). High serum and ascites IGF-2 levels were associated with increased risk of mortality (HR: 2.01 (1.22–3.30) and HR: 1.78 (1.24–2.54), respectively). Similarly, serum PAPP-A2 was associated with mortality (HR: 1.26 (1.08–1.48)). Our findings demonstrate the presence and activity of the IGF system in the local tumor ecosystem, which is likely a characteristic feature of malignant disease and plays a role in its peritoneal dissemination. The potential clinical implications are supported by our finding that serum levels of the proteins are associated with patient prognosis.
Highly Concentrated Stabilized Hybrid Complexes of Hyaluronic Acid: Rheological and Biological Assessment of Compatibility with Adipose Tissue and Derived Stromal Cells towards Regenerative Medicine
Authors: Vassallo Valentina , Di Meo Celeste , Alessio Nicola , La Gatta Annalisa , Ferraro Giuseppe Andrea , Nicoletti Giovanni Francesco , Schiraldi Chiara
Published: February 2024

Cells and extracts derived from adipose tissue are gaining increasing attention not only in plastic surgery and for aesthetic purposes but also in regenerative medicine. The ability of hyaluronan (HA) to support human adipose stromal cell (hASC) viability and differentiation has been investigated. However, the compatibility of adipose tissue with HA-based formulation in terms of biophysical and rheological properties has not been fully addressed, although it is a key feature for tissue integration and in vivo performance. In this study, the biophysical and biochemical properties of highly concentrated (45 mg/mL) high/low-molecular-weight HA hybrid cooperative complex were assessed with a further focus on the potential application in adipose tissue augmentation/regeneration. Specifically, HA hybrid complex rheological behavior was observed in combination with different adipose tissue ratios, and hyaluronidase-catalyzed degradation was compared to that of a high-molecular-weight HA (HHA). Moreover, the HA hybrid complex’s ability to induce in vitro hASCs differentiation towards adipose phenotype was evaluated in comparison to HHA, performing Oil Red O staining and analyzing gene/protein expression of PPAR-γ, adiponectin, and leptin. Both treatments supported hASCs differentiation, with the HA hybrid complex showing better results. These outcomes may open new frontiers in regenerative medicine, supporting the injection of highly concentrated hybrid formulations in fat compartments, eventually enhancing residing staminal cell differentiation and improving cell/growth factor persistence towards tissue regeneration districts.
Production of Pumilarin and a Novel Circular Bacteriocin, Altitudin A, by Bacillus altitudinis ECC22, a Soil-Derived Bacteriocin Producer
Authors: Lafuente Irene , Sevillano Ester , Peña Nuria , Cuartero Alicia , Hernández Pablo E. , Cintas Luis M. , Muñoz-Atienza Estefanía , Borrero Juan
Published: February 2024

The rise of antimicrobial resistance poses a significant global health threat, necessitating urgent efforts to identify novel antimicrobial agents. In this study, we undertook a thorough screening of soil-derived bacterial isolates to identify candidates showing antimicrobial activity against Gram-positive bacteria. A highly active antagonistic isolate was initially identified as Bacillus altitudinis ECC22, being further subjected to whole genome sequencing. A bioinformatic analysis of the B. altitudinis ECC22 genome revealed the presence of two gene clusters responsible for synthesizing two circular bacteriocins: pumilarin and a novel circular bacteriocin named altitudin A, alongside a closticin 574-like bacteriocin (CLB) structural gene. The synthesis and antimicrobial activity of the bacteriocins, pumilarin and altitudin A, were evaluated and validated using an in vitro cell-free protein synthesis (IV-CFPS) protocol coupled to a split-intein-mediated ligation procedure, as well as through their in vivo production by recombinant E. coli cells. However, the IV-CFPS of CLB showed no antimicrobial activity against the bacterial indicators tested. The purification of the bacteriocins produced by B. altitudinis ECC22, and their evaluation by MALDI-TOF MS analysis and LC-MS/MS-derived targeted proteomics identification combined with massive peptide analysis, confirmed the production and circular conformation of pumilarin and altitudin A. Both bacteriocins exhibited a spectrum of activity primarily directed against other Bacillus spp. strains. Structural three-dimensional predictions revealed that pumilarin and altitudin A may adopt a circular conformation with five- and four-α-helices, respectively.
Biomimetic Diatom Biosilica and Its Potential for Biomedical Applications and Prospects: A Review
Authors: Min Ki Ha , Kim Dong Hyun , Youn Sol , Pack Seung Pil
Published: February 2024

Diatom biosilica is an important natural source of porous silica, with three-dimensional ordered and nanopatterned structures referred to as frustules. The unique features of diatom frustules, such as their high specific surface area, thermal stability, biocompatibility, and adaptable surface chemistry, render diatoms valuable materials for high value-added applications. These attributes make diatoms an exceptional cost-effective raw material for industrial use. The functionalization of diatom biosilica surface improves its biophysical properties and increases the potential applications. This review focuses on the potential uses of diatom biosilica including traditional approaches and recent progress in biomedical applications. Not only well-studied drug delivery systems but also promising uses on bone regeneration and wound healing are covered. Furthermore, considerable aspects and possible future directions for the use of diatom biosilica materials are proposed to develop biomedical applications and merit further exploration.
The Alarmin Triad—IL-25, IL-33, and TSLP—Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria
Authors: Dobrican-Băruța Carmen-Teodora , Deleanu Diana Mihaela , Muntean Ioana Adriana , Nedelea Irena , Bălan Radu-Gheorghe , Filip Gabriela Adriana , Procopciuc Lucia Maria
Published: February 2024

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33’s correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.
Are TaNAC Transcription Factors Involved in Promoting Wheat Yield by cis-Regulation of TaCKX Gene Family?
Authors: Iqbal Adnan , Bocian Joanna , Przyborowski Mateusz , Orczyk Wacław , Nadolska-Orczyk Anna
Published: February 2024

NAC transcription factors (TFs) are one of the largest TF families in plants, and TaNACs have been known to participate in the regulation of the transcription of many yield-regulating genes in bread wheat. The TaCKX gene family members (GFMs) have already been shown to regulate yield-related traits, including grain mass and number, leaf senescence, and root growth. The genes encode cytokinin (CK) degrading enzymes (CKXs) and are specifically expressed in different parts of developing wheat plants. The aim of the study was to identify and characterize TaNACs involved in the cis-regulation of TaCKX GFMs. After analysis of the initial transcription factor data in 1.5 Kb cis-regulatory sequences of a total of 35 homologues of TaCKX GFMs, we selected five of them, namely TaCKX1-3A, TaCKX22.1-3B, TaCKX5-3D, TaCKX9-1B, and TaCKX10, and identified five TaNAC genes: TaNACJ-1, TaNAC13a, TaNAC94, TaNACBr-1, and TaNAC6D, which are potentially involved in the cis-regulation of selected TaCKX genes, respectively. Protein feature analysis revealed that all of the selected TaNACs have a conserved NAC domain and showed a stable tertiary structure model. The expression profile of the selected TaNACs was studied in 5 day-old seedling roots, 5–6 cm inflorescences, 0, 4, 7, and 14 days-after-pollination (DAP) spikes, and the accompanying flag leaves. The expression pattern showed that all of the selected TaNACs were preferentially expressed in seedling roots, 7 and 14 DAP spikes, and flag leaves compared to 5–6 cm inflorescence and 0 and 4 DAP spikes and flag leaves in Kontesa and Ostka spring wheat cultivars (cvs.). In conclusion, the results of this study highlight the potential role of the selected TaNACs in the regulation of grain productivity, leaf senescence, root growth, and response to various stresses.
Evidence That Aquaporin 11 (AQP11) in the Spiny Dogfish (Squalus acanthias) May Represent a Pseudogene
Authors: Cutler Christopher P. , Canicatti Meghan E. , Omoregie Esosa
Published: February 2024

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148 bp fragment showing particularly strong amplification in gill and intestine. It was sequenced and represented a piece of the AQP11 gene. However, as the fragment may have resulted from contaminating genomic DNA (in total RNA used to make cDNA), 5′ and 3′ RACE were performed to amplify the two ends of the putative cDNA. Furthermore, 5′ and 3′ RACE amplifications depend on the presence of a 5′ cap nucleotide and a poly A tail, respectively on the putative AQP11 mRNA. Hence, successful amplification was only possible from cDNA and not genomic DNA. Nested RACE amplifications were performed using gill and intestinal RACE cDNA, but none of the DNA fragments sequenced were AQP11. Consequently, the spiny dogfish AQP11 gene may represent a pseudogene.
Role of Oxygen and Its Radicals in Peripheral Nerve Regeneration: From Hypoxia to Physoxia to Hyperoxia
Authors: André-Lévigne Dominik , Pignel Rodrigue , Boet Sylvain , Jaquet Vincent , Kalbermatten Daniel F. , Madduri Srinivas
Published: February 2024

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.
T Cell Responses in Pregnant Women Who Received mRNA-Based Vaccination to Prevent COVID-19 Revealed Unknown Exposure to the Natural Infection and Numerous SARS-CoV-2-Specific CD4- CD8- Double Negative T Cells and Regulatory T Cells
Authors: Chambers Christina D. , Song Jaeyoon , da Silva Antunes Ricardo , Sette Alessandro , Franco Alessandra
Published: February 2024

We studied T-cell responses to SARS-CoV-2 in 19 pregnant subjects at different gestational weeks who received three doses of mRNA-based vaccination to prevent COVID-19. SARS-CoV-2 peptide pools were used for T-cell recognition studies: peptides were 15 amino acids long and had previously been defined in COVID-19-convalescent subjects. T-cell activation was evaluated with the AIM assay. Most subjects showed coordinated, spike-specific CD4+ and CD8+ T-cell responses and the development of T cell memory. Non-spike-specific T cells in subjects who were not aware of previous COVID-19 infection suggested a prior undetected, asymptomatic infection. CD4- CD8- double negative (DN) T cells were numerous, of which a percentage was specific for SARS-CoV-2 spike peptides. Regulatory T cells (Treg), both spike- and non-spike-specific, were also greatly expanded. Two Treg populations were defined: a population differentiated from naïve T cells, and pTreg, reverting from pro-inflammatory T cells. The Treg cells expressed CCR6, suggesting homing to the endometrium and vaginal epithelial cells. The pregnant women responded to SARS-CoV-2 vaccination. Asymptomatic COVID-19 was revealed by the T cell response to the non-spike peptides. The numerous DN T cells and Treg pointed our attention to new aspects of the adaptive immune response in vaccine recipients.
Managing Colorectal Cancer from Ethology to Interdisciplinary Treatment: The Gains and Challenges of Modern Medicine
Authors: Berbecka Monika , Berbecki Maciej , Gliwa Anna Maria , Szewc Monika , Sitarz Robert
Published: February 2024

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract, which has become a serious threat to human health worldwide. This article exhaustively reviews colorectal cancer’s incidence and relevance, carcinogenesis molecular pathways, up-to-date treatment opportunities, prophylaxis, and screening program achievements, with attention paid to its regional variations and changes over time. This paper provides a concise overview of known CRC risk factors, including familial, hereditary, and environmental lifestyle-related risk factors. The authors take a closer look into CRC’s molecular genetic pathways and the role of specific enzymes involved in carcinogenesis. Moreover, the role of the general practitioner and multidisciplinary approach in CRC treatment is summarized and highlighted based on recent recommendations and experience. This article gives a clear understanding and review of the gains and challenges of modern medicine towards CRC. The authors believe that understanding the current patterns of CRC and its revolution is imperative to the prospects of reducing its burden through cancer prevention and cancer-adjusted treatment.