bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Impact of Chlorogenic Acid Content and Cellulose Nanoparticles on Sunflower Protein-Based Emulsions and Films
Authors: Gomes Andresa , Cangussu Lais Brito , Cunha Rosiane Lopes , Oliveira Leandro Soares de , Franca Adriana Silva , Costa Ana Letícia Rodrigues
Published: February 2025

This study explores how varying chlorogenic acid levels (low—yellowish, Y; high—greenish, G) in sunflower proteins (SFs) affect the properties of eugenol-loaded oil-in-water emulsions and the resulting films, while examining the interaction of cellulose nanoparticles (from commercial (CNC) and banana peel sources (CNF)) with the film-forming matrix. This research fills gaps in literature by demonstrating how interactions among proteins, lipids, phenolic compounds, and cellulose nanoparticles influence film properties. The high chlorogenic acid content in SF reduced electrostatic repulsion between protein molecules, causing aggregation, oil droplet flocculation, and increased emulsion viscosity. The mechanical properties of emulsion-based films were significantly lower than those made with SF dispersions. Films made from low chlorogenic acid (yellowish SF) emulsions showed lower tensile strength and Young’s modulus but higher elongation at break compared to those made from high chlorogenic acid (greenish SF) emulsions. Water vapor permeability (WVP) decreased in films containing oil phases, but adding cellulose nanoparticles increased WVP. Despite this, the cellulose nanoparticles could not fully overcome the negative effects of lipid–protein interactions on mechanical properties and WVP. However, films containing eugenol exhibited significant antioxidant activity. The findings provide insights into developing sustainable, active packaging with antioxidant functionality and reduced environmental impact, opening new avenues for applications in food and other sectors requiring eco-friendly materials.
AOX Affects the Synthesis of Polysaccharides by Regulating the Reactive Oxygen Species in Ganoderma lucidum
Authors: Zhu Ruiying , Zhang Lele , Wu Longxi , Liu Jingshuo , Zhang Jie , Li Jian , Song Kejing , Han Peipei
Published: February 2025

Alternative oxidase (AOX) is a terminal oxidase in the mitochondrial electron transport chain that does not contribute to the generation of ATP. It plays a critical role in maintaining the balance between reactive oxygen species (ROS) production and intracellular redox homeostasis within the mitochondria. In the study, overexpression and knockdown approaches were employed to investigate the function of AOX. AOX-silenced strains (AOXi3 and AOXi25) and AOX-overexpressed strains (OE-AOX2 and OE-AOX21) were constructed. The ROS level and transcription level of the antioxidant-system-related genes, including phosphoglucomutase (pgm) and phosphomannose isomerase (pmi), were differentially upregulated in silenced strains, whereas the opposite effect was observed in the AOX-overexpressed strains. Compared with the wild type (WT), the polysaccharide production of AOXi25 was significantly increased by approximately 38%, while OE-AOX21 was significantly decreased by 80%. Six extracellular polysaccharides (EPSs) were extracted and purified from the WT, OE-AOX21, and AOXi25 strains. These EPSs, consisting of both neutral and acidic polysaccharides, were composed of five different monosaccharides in varying proportions. The average relative molecular masses were 1.68 × 103, 2.66 × 103, 1.67 × 103, 2.42 × 103, 1.12 × 103, and 2.35 × 103 kDa, respectively. Antioxidant assays demonstrated that all EPSs exhibited strong free radical scavenging activity with the acidic polysaccharide from AOXi25 showing the highest efficiency in ABTS+ scavenging. These findings highlight the significant role of AOX-derived ROS in regulating polysaccharide synthesis and accumulation in Ganoderma lucidum.
Characteristic Changes and Potential Markers of Flavour in Raw Pu-Erh Tea with Different Ageing Cycles Analysed by HPLC, HS-SPME-GC-MS, and OAV
Authors: Xu Jiayi , Deng Xiujuan , Wu Yamin , Zhou Miao , Du Cen , Wang Qiaomei , Xia Yuxin , He Junjie , Yuan Wenxia , Wu Wendou , Li Hongxu , Wang Yankun , Li Tong , Wang Baijuan
Published: February 2025

To investigate the flavour evolution mechanism of raw Pu-erh tea (RPT) during storage, the volatile and non-volatile compounds of RPT with different storage years (1–10 years) from the same raw material origin, manufacturer, and storage location in Wenshan Prefecture, Yunnan Province, were systematically analysed by HPLC, HS-SPME-GC-MS, and OAV. The results showed that both cluster analyses based on non-volatile and volatile compounds could classify RPT of different storage years into three ageing cycles, with key turning points in the third and eighth years of storage, which is also accompanied by the colour changing from green to orange or brown, the aroma changing from a faint scent to woody and ageing, the astringency diminishing, and the sweet and mellow increasing. Theophylline was identified as the potential marker of RPT stored 1–3 years, while (−)-catechin gallate, (−)-gallocatechin gallate, quercetin, and rutin as those for a storage of 9–10 years. The volatile compounds indicate a general trend of an initial increase followed by a decrease. Forty-four key aroma compounds (OAV ≥ 1) were identified. Eucalyptol, β-Caryophyllene, 2-Amylfuran, Copaene, Estragole, and α-Terpinene originated as potential markers for RPT stored 1–3 years, while (Z)-Linalool oxide (furanoid), α-Terpineol, Terpinen-4-ol, and cis-Anethol were for RPT stored 8–10 years. This study revealed the flavour characteristics and quality changes of RPT over the course of storage, and constructed a sensory flavour wheel, providing theoretical underpinnings for the quality control and assessment of RPT.
Certain Analytic Solutions for Time-Fractional Models Arising in Plasma Physics via a New Approach Using the Natural Transform and the Residual Power Series Methods
Authors: Freihat Asad , Alabedalhadi Mohammed , Al-Omari Shrideh , Alhazmi Sharifah E. , Momani Shaher , Al-Smadi Mohammed
Published: February 2025

This paper studies three time-fractional models that arise in plasma physics: the modified Korteweg–deVries–Zakharov–Kuznetsov equation, the stochastic potential Korteweg–deVries equation, and the forced Korteweg–deVries equation. These equations are significant in plasma physics for modeling nonlinear ion acoustic waves and thus helping us to understand wave dynamics in plasmas. We introduce a new approach that relies on a new fractional expansion in the natural transform space and residual power series method to construct analytical solutions to the governing models. We investigate the theoretical analysis of the proposed method for these equations to expose this approach’s applicability, efficiency, and effectiveness in constructing analytical solutions to the governing equations. Moreover, we present a comparative discussion between the solutions derived during the work and those given in the literature to confirm that the proposed approach generates analytical solutions that rapidly converge to exact solutions, which proves the effectiveness of the proposed method.
Correction: Sadeghi et al. lncRNA–miRNA–mRNA ceRNA Network Involved in Sheep Prolificacy: An Integrated Approach. Genes 2022, 13, 1295
Authors: Sadeghi Masoumeh , Bahrami Abolfazl , Hasankhani Aliakbar , Kioumarsi Hamed , Nouralizadeh Reza , Abdulkareem Sarah Ali , Ghafouri Farzad , Barkema Herman W.
Published: February 2025

In the original publication [...]
Developmental Trajectories of Intrinsic Capacity Among Older Adults: Results from the China Longitudinal Study of Aging
Authors: Zhou Jia , Chang Hui , Wang Zhiwen
Published: February 2025

Background: Previous studies have shown that intrinsic capacity changes over time and can independently predict adverse outcomes such as mortality and care dependence in older adults. However, explorations of the heterogeneity in the developmental trajectories of intrinsic capacity are limited. Aim: This study aimed to identify potential intrinsic capacity trajectory groups and the factors impacting different trajectory groups among older adults. Methods: We utilized data from 2454 older adults aged 60 and above, sourced from the Chinese Longitudinal Healthy Longevity Survey. Our analyses were conducted using growth mixture modeling, chi-square tests, and multinomial logistic regression analysis. Results: We identified four intrinsic capacity trajectory groups among older adults in China: low-level intrinsic capacity (3.2%), medium-level increasing intrinsic capacity (13.0%), medium-level decreasing intrinsic capacity (12.0%), and stable high intrinsic capacity (71.8%). Age was an influencing factor of the medium-level increasing intrinsic capacity, medium-level decreasing intrinsic capacity, and stable high intrinsic capacity trajectory groups. Compared to individuals in the low-level intrinsic capacity trajectory group, individuals in the medium-level decreasing intrinsic capacity group were more likely to regularly exercise and participate in social activity, and those in the stable high intrinsic capacity group were more likely to be male, drink, participate in social activity, and have good self-rated health. Conclusions: Understanding the developmental trajectories of the intrinsic capacity of the older adults can contribute to formulating personalized intervention planning. We identified four intrinsic capacity trajectories in a cohort of older adults in China, which highlights significant heterogeneity in intrinsic capacity development. Our findings suggest that age, gender, exercise, drinking, social activity, and self-rated health of older adults have important effects on different intrinsic capacity development trajectories.
Transfusion Thresholds and Risk Factors of Acute Kidney Injury in Gastrointestinal Oncology Surgery: Insights from a Retrospective Study
Authors: Ma Shuai , He Qi , Yang Chengcan , Zhou Zhiyuan , He Yining , Yu Chaoran , Yao Danhua , Zheng Lei , Huang Yuhua , Li Yousheng
Published: February 2025

Objectives: To identify transfusion thresholds and risk factors for acute kidney injury (AKI) in gastrointestinal oncology surgery, enhancing early intervention and improving postoperative outcomes. Methods: From 2018 to 2022, 765 patients with gastric or colorectal cancer who underwent major gastrointestinal surgery were retrospectively enrolled. The primary outcome was AKI development within 7 days postoperatively. Clinicopathological characteristics and short-term outcomes were recorded and compared. Results: Of all enrolled patients, 39 (5.1%) developed AKI. Patients with AKI were predominantly older and had more preoperative comorbidities, lower levels of preoperative hemoglobin and serum albumin, but higher levels of blood urea nitrogen and serum creatinine (SCr). Patients developing AKI experienced higher rates of in-hospital complications (overall: 48.3% vs. 14.2%, p < 0.001), prolonged hospital stays (25.4 ± 22.5 days vs. 12.3 ± 7.9 days, p < 0.001), increased intensive care unit (ICU) admissions (53.8% vs. 22.5%, p < 0.001), and higher rates of 30-day re-admission (13.9% vs. 2.4%, p = 0.003). Significant AKI risk factors included age (per 10 years, OR: 1.567, 95% CI: 1.103–2.423, p = 0.043), preoperative SCr (per 10 μmol/L, OR: 1.173, 95% CI: 1.044–1.319, p = 0.007), intraoperative RBC transfusion (per 1000 mL, OR: 1.992, 95% CI: 1.311–3.027, p = 0.001 with a significant surge in AKI risk at transfusions exceeding 1500 mL), patient-controlled analgesia (protective, OR:0.338, 95% CI: 0.163–0.928, p = 0.033), and diuretic use (OR: 5.495, 95% CI: 1.720–17.557, p = 0.004). Conclusions: Early intervention is essential for patients with preoperative low perfusion or anemia, with particular emphasis on moderating interventions to avoid fluid overload while carefully avoiding nephrotoxic medications, thereby improving postoperative outcomes.
Trends in Physical Activity Research on Tobacco and/or Alcohol: A Bibliometric Analysis
Authors: Castillo-Paredes Antonio , del Val Martín Pablo , Ferrari Gerson
Published: February 2025

Background/Objectives: Physical activity allows the enjoyment of personal health benefits in those who practice it, including the possibility of modifying behavioral risk factors such as tobacco and alcohol consumption. These risk factors are responsible for the development of non-communicable diseases, which are preventable and controllable. The scientific field on this object of study has grown in recent years. The main objective of this study was to perform a scientific mapping to explore the trend of annual publications, and to analyze and identify the thematic categories, the authors, countries and journals with the highest number of papers, the most referenced papers and authors, and the most used keywords in research related to physical activity and tobacco and/or alcohol consumption. Methods: Through a bibliometric analysis based on traditional bibliometric laws on the scientific documentation related to the subject and indexed in the Main Collection of the Web of Science. The DeSolla Price Law was used to analyze the trend of annual publications, using the coefficient of determination R2. Lotka’s law was applied to identify prolific authors, Bradford’s law to highlight the most frequent publication sources, the h-index to identify the most cited articles and Zipf’s law to highlight the keywords most used in research. Results: A total of 538 documents were analyzed. The trend followed by annual publications is in an exponential growth phase. Adrian Taylor and Michael Ussher were identified as prolific authors. USA and Preventive Medicine were the country and journal with the highest number of publications. The most frequently used words were physical activity, smoking, exercise, alcohol, obesity, and smoking cessation. Conclusions: This bibliometric review identified an exponential growth from 1994 to date of research related to physical activity and tobacco and/or alcohol consumption. It allowed us to identify trends and guide the development of future research in these or new related areas.
Subjectivity of Obese Female Adolescents in South Korea Regarding Ego-Types and Characteristics
Authors: Joung Kihong , Jeon Wonjae
Published: February 2025

Background/Objectives: The current study aims to explore the subjective ego types and characteristics of obese female adolescents in South Korea, providing insights into their self-perception and psychosocial challenges. Methods: Utilizing Q-methodology, a total of 49 Q-statements were derived from a comprehensive Q-population. From these, 20 adolescents diagnosed with obesity were selected as the P-Sample. Q-sorting was conducted, and the data collected were analyzed using the PQ Method software version 2.35, employing centroid factor analysis and varimax rotation. Results: The results revealed five distinct types, accounting for a cumulative explanatory variance of 63%. Type 1 (N = 5) was characterized as “obsession with weight loss”. Type 2 (N = 3) was identified as “overreacting to peer gaze”. Type 3 (N = 6) was labeled “lack of confidence in daily life”. Type 4 (N = 4) was described as “difficulty adapting to school life”. Finally, Type 5 (N = 2) was characterized as “passivity in physical activity”. Furthermore, the consensus statements among each type were examined in Q4 and Q7. Conclusions: These findings provide insights into the self-perception of obese female adolescents, emphasizing the need for tailored psychological interventions to improve their self-image and well-being.
On the Birth of Modern Chemistry: I—The Atomic–Molecular Theory from Dalton to Avogadro
Authors: Salvi Pier Remigio
Published: February 2025

The purpose of this paper is to review the basic steps in the development of the atomic–molecular theory with the support of the original documentation. The most important contributions are examined, from the first intimation of the theory by Dalton to the Avogadro hypothesis, intended to reconcile empirical relations observed by Gay-Lussac in gaseous reactions with the atomistic ideas. The genesis and the structure of Dalton’s theory are described, and attention is focused on the rules of the greatest simplicity by means of which the relative weights and sizes of elementary and compounds atoms were determined. The first striking achievements are outlined. A peculiar trait of the Daltonian principles is represented by the rejection of a simple relation between specific gravities of elastic fluids and weights of the ultimate particles. On the contrary, the fixed (and small) ratios of reacting volumes in gaseous reactions, a result discovered by Gay-Lussac, suggest that particles combine according to simple numbers. The equal volume/equal number of particles hypothesis was a substitute better than Dalton’s rules for the determination of the atomic weights and led to the prediction of elementary polyatomic molecules.
The Applicability of the Demirjian and Willems Standards to Age Estimation of 6–9-Year-Old Portuguese Children
Authors: Vieira Ivo , Pereira Maria Lurdes , Caldas Inês Morais
Published: February 2025

This study evaluates the applicability of Demirjian and Willems’ methods for age estimation in Portuguese children aged 6–9 years based on orthopantomographs (OPGs). The main objective was to compare the precision of both methods in estimating chronological age (CA). This study analyzed 160 OPGs, equally distributed by sex, and the dental age (DA) was calculated twice, using both methodologies. The findings reveal that Demirjian’s method consistently overestimated the chronological age by an average of 1.47 years for males and 1.45 years for females. Similarly, the Willems method also overestimated the age but to a lesser extent, with mean differences of 1.18 years for males and 0.91 years for females. Statistical analysis confirmed that both methods significantly overestimate age, with the most considerable discrepancies observed in 8-year-old individuals. Despite the Willems method providing slightly more accurate results, neither method was reliable, particularly for male subjects. This study highlights the need for further refinement of these methods, considering their tendency to overestimate age, especially in specific age groups. This research improves age estimation techniques in forensic and clinical settings, especially within the Portuguese pediatric population.
Endothelial Dysfunction Markers Correlate with the Time Since Completion of Tuberculosis Treatment and the Number of Previous Tuberculosis Episodes
Authors: Jumaar Chrisstoffel , Jacobs Steve , Payne Carmen , Sanni Olakunle , Louw Elize , Baines Nicola , Maree David , Botha Benjamin , Feyasa Merga Belina , Strijdom Hans , Allwood Brian , Maarman Gerald J.
Published: February 2025

Background: Despite “successful” treatment, some lung tuberculosis (TB) patients develop long-term lung impairments that includes damage to the parenchyma and reduced function, which may predispose them to diseases like pulmonary hypertension. However, this is not well understood. Therefore, we investigated whether previous or current TB patients would display elevated biomarkers of endothelial dysfunction and vascular remodeling. Methods: We performed assays for ADMA, VCAM-1, VEGF, angiopoietin-1, TBARS, NT-pro-BNP, and cardiac troponin-I. We further stratified the patients based on 1, 2, 3, and >3 previous TB episodes, and 1–5 yrs, 5–10 yrs, 10–15 yrs and >15 yrs after the last TB treatment completion. We also assessed correlations between the biomarkers and the number of previous TB episodes or the time since the completion of the last TB treatment. Results: ADMA was 70 times higher, VEGF was 2000 times higher and angiopoietin-1 was 6500 times higher than the normal range. NT-pro-BNP and cardiac troponin-I were undetected, and TBARS levels were low. There was a positive linear relationship between the number of previous TB episodes and angiopoietin-1, and between VEGF and the number of previous TB episodes. ADMA, VCAM-1 and TBARS exhibited a weak and negative linear association with the number of previous TB episodes. A negligible negative linear association was observed between the time since the completion of the last TB treatment and angiopoietin-1, VEGF and ADMA. Conclusions: Therefore, having >1 previous TB episode, despite the successful completion of TB treatment, associates with an increased risk of endothelial dysfunction/angiogenesis or vascular remodeling.
Non-Communicable Diseases, Longevity, and Health Span: A Hong Kong Perspective
Authors: Woo Jean , Marmot Michael
Published: February 2025

The health of different countries evolves in parallel with their economic development. Communicable diseases play a more prominent role in low-income countries compared with high-income countries, while non-communicable diseases (NCDs) have become dominant in developing and developed economies. This transition has been accompanied by public health efforts to prevent NCDs, resulting in improvements in total life expectancy at birth (TLE). It is recognized that health determinants are not confined to healthcare systems, but that social determinants play a key role in health inequalities. The rapid increase in life expectancy at birth has led to increasing numbers of older adults, where health inequalities are accentuated. The current UN Decade of Healthy Aging calls for a life-course approach to building intrinsic capacity, maintaining function, and avoiding dependency with age instead of avoiding mortality and morbidity. TLE in Hong Kong is one of the highest in the world as a result of public health preventive efforts and an essentially free hospital system. However, the increase in TLE has not been accompanied by the same magnitude of increase in health span, resulting in an increasing dependency burden. Geography, culture, dietary and smoking habits, physical activity, urban planning, and neighbourhood cohesion are some of the social determinants affecting TLE and also health inequalities. With population ageing, it would be appropriate to focus on the social determinants affecting health span to maintain functional independence rather than prolonging life. A whole-of-society response instead of relying solely on the adaptation of health and social care systems would be needed, together with more nuanced metrics to measure health span.
National Implementation of Perinatal Mental Health Treatment—The MumSpace Digital Stepped-Care Model
Authors: Milgrom Jeannette , Garner Brydie , Rodrigues Andre , Fisher Jane , Borninkhof Julie , Kavanagh David , Gemmill Alan W.
Published: February 2025

Perinatal depression is highly prevalent, yet there is a very low rate of treatment uptake and help-seeking. The MumSpace Initiative was funded by the Australian government to invest in digital stepped-care treatments and support for perinatal depression, to improve mental health outcomes and national access. This paper describes the reach of the MumSpace initiative as a one-stop shop offering perinatal depression treatments with a solid evidence base (MumMoodBooster programmes), supported by a prevention programme addressing modifiable risk factors through a smartphone application (MindMum) as well as evidence-based universal prevention programmes. We have brought together multi-skilled teams and a Perinatal Depression Consortium to deliver the programmes and address changing technology. The effectiveness of MumSpace was evaluated through systematic monitoring of consumer reach: data analysis of website traffic and resource uptake. MumSpace has successfully sustained engagement, attracting over 275,000 visits since its launch in 2017, with the number of visitors to the website increasing year on year. The central treatment tools, MumMoodBooster and Mum2BMoodBooster, have reached over 10,000 Australian women, largely through self-referral. Despite the development of a portal for direct clinician referral and monitoring, continuing challenges for implementation involve integrating digital treatments into traditional services and recruiting professionals to directly engage mothers.
Trastuzumab Decreases the Expression of G1/S Regulators and Syndecan-4 Proteoglycan in Human Rhabdomyosarcoma
Authors: Szabo Dora Julianna , Toth Eniko , Szabo Kitti , Hegedus Zsofia Kata , Bozsity-Farago Noemi , Zupko Istvan , Rovo Laszlo , Xiao Xue , Xu Lin , Keller-Pinter Aniko
Published: February 2025

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, arises from skeletal muscle cells that fail to differentiate terminally. Two subgroups of RMS, fusion-positive and fusion-negative RMS (FPRMS and FNRMS, respectively), are characterized by the presence or absence of the PAX3/7-FOXO1 fusion gene. RMSs frequently exhibit increased expression of human epidermal growth factor receptor-2 (HER2). Trastuzumab is a humanized monoclonal antibody targeting HER2, and its potential role in RMS treatment remains to be elucidated. Syndecan-4 (SDC4) is a heparan sulfate proteoglycan (HSPG) affecting myogenesis via Rac1-mediated actin remodeling. Previously, we demonstrated that the SDC4 gene is amplified in 28% of human FNRMS samples, associated with high mRNA expression, suggesting a tumor driver role. In this study, after analyzing the copy numbers and mRNA expressions of other HSPGs in human RMS samples, we found that in addition to SDC4, syndecan-1, syndecan-2, and glypican-1 were also amplified and highly expressed in FNRMS. In RD (human FNRMS) cells, elevated SDC4 expression was accompanied by low levels of phospho-Ser179 of SDC4, leading to high Rac1-GTP activity. Notably, this high SDC4 expression in RD cells decreased following trastuzumab treatment. Trastuzumab decreased the levels of G1/S checkpoint regulators cyclin E and cyclin D1 and reduced the cell number; however, it also downregulated the cyclin-dependent kinase inhibitor p21. The level of MyoD, a transcription factor essential for RMS cell survival, also decreased following trastuzumab administration. Our findings contribute to the understanding of the role of SDC4 in FNRMS. Since HER2 is expressed in about half of RMSs, the trastuzumab-mediated changes observed here may have therapeutic implications.
The Regenerative Marriage Between High-Density Platelet-Rich Plasma and Adipose Tissue
Authors: Everts Peter A. , Podesta Luga , Lana José Fabio , Shapiro George , Domingues Rafael Barnabé , van Zundert Andre , Alexander Robert W.
Published: February 2025

The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care. Healthcare professionals can employ ABPs to mimic the classical wound healing cascade, initiate the angiogenesis cascade, and induce tissue regenerative pathways, aiming to restore the integrity and function of damaged tissues. In this review, we will address combining autologous HD-PRP with adipose tissue, in particular the tissue stromal vascular fraction (t-SVF), as we believe that this biocellular combination demonstrates a synergistic effect, where the HD-PRP constituents enhance the regenerative potential of t-SVF and its adipose-derived mesenchymal stem cells (AD-MSCs) and pericytes, leading to improved functional tissue repair, tissue regeneration, and wound healing in variety of clinical applications. We will address some relevant platelet bio-physiological aspects, since these properties contribute to the synergistic effects of combining HD-PRP with t-SVF, promoting overall better outcomes in chronic inflammatory conditions, soft tissue repair, and tissue rejuvenation.
NapR Regulates the Expression of Phosphoserine Aminotransferase SerC to Modulate Biofilm Formation and Resistance to Serine Stress of Mycobacteria
Authors: Guo Minhao , Ling Xiaocui , He Linzhao , Gou Yukuo , Li Zhun , Li Weihui
Published: February 2025

Mycobacterium tuberculosis is a formidable pathogen capable of establishing persistent infections within macrophages. To survive and thrive within the host environment, it has evolved intricate regulatory networks, including a diverse array of transcription factors that enable adaptation to various stresses encountered within the host. However, the mechanisms by which transcription factors regulate biofilm formation in M. tuberculosis remain incompletely understood. This study aimed to investigate the role of serC, encoding phosphoserine aminotransferase, and its regulation by NapR, a transcription factor, in mycobacterial physiology. NapR regulates serC through directly binding to its promoter. Notably, the regulatory effect and corresponding phenotypes vary due to distinct binding affinities of NapR for the serC promoter in different mycobacterial species. In Mycobacterium smegmatis, NapRMsm positively regulates biofilm formation, growth on solid media, and the transition from microcolonies to microcolonies by activating serCMsm. In the BCG vaccine, on the contrary, NapRBCG represses serCBCG, thus negatively regulating colony size and alleviating the growth inhibition caused by high concentrations of serine. Furthermore, proteomic analysis suggested NapR serves as a global transcriptional regulator in BCG vaccine strains by simultaneously modulating four metabolic pathways. These findings underscore the complex and strain-specific regulatory mechanisms governing serine metabolism in mycobacteria and provide valuable insights into the interplay between metabolism, gene regulation, and bacterial physiology.
A Leg Cuticle Protein Enhances the Resistance of Anopheles sinensis Mosquitoes to Deltamethrin
Authors: Li Lin , Gu Ling , Tu Lei , Deng Si-Jia , Hu Ju-Ping , Zhang Zi-Ye , Li Ju-Lin , Zhang Mei-Chun , Cao Jun , Tang Jian-Xia , Zhu Guo-Ding
Published: February 2025

Insecticide resistance in mosquitoes has become a severe impediment to global vector control and manifests as decreased insecticide effectiveness. The role of target site mutations and detoxification enzymes as resistance markers has been documented in mosquitoes; however, the emergence of complex resistant phenotypes suggest the occurrence of additional mechanisms. Cuticular proteins (CPs) are key constituents of the insect cuticle, and play critical roles in insect development and insecticide resistance. In this study, via electron microscopy we observed that the leg cuticle thickness in deltamethrin-resistant (DR) Anopheles sinensis mosquitoes was significantly greater than that measured in deltamethrin-susceptible (DS) An. sinensis. Transcription analysis revealed that cuticle proteins were enriched in the legs, including members of the CPR, CPAP, and CPF families. Further comparisons revealed the specific overexpression of four CP genes in the legs of DR An. sinensis; whose expression levels increased after treatment with deltamethrin. The RNAi-mediated silencing of one CP gene, AsCPF1, resulted in a significant decrease in the leg cuticle thickness of DR mosquitoes and significantly elevated the mortality rate when exposed to deltamethrin. These findings suggest that alterations in the An. sinensis leg cuticle contribute to the insecticide resistance phenotype. AsCPF1 is thereby a target study molecule for investigation of its mode of action, and broader attention should be paid to the role of mosquito legs in the development of insecticide resistance.
Molecular Approaches to Treating Chronic Obstructive Pulmonary Disease: Current Perspectives and Future Directions
Authors: Vu Sheryl-Phuc , Veit Kaleb , Sadikot Ruxana T.
Published: February 2025

Chronic obstructive pulmonary disease (COPD) is a clinical syndrome that presents as airflow limitation with poor reversibility accompanied by dynamic hyperinflation of the lung. It is a complex disease with chronic inflammatory airway changes caused by exposure to noxious particles or gases, such as cigarette smoke. The disease involves persistent inflammation and oxidative stress, perpetuated by frequent exacerbations. The prevalence of COPD is on the rise, with the prediction that it will be the leading cause of morbidity and mortality over the next decade. Despite the global burden of COPD and its associated morbidity and mortality, treatment remains limited. Although the understanding of the pathogenesis of COPD has increased over the last two decades, molecular approaches to develop new therapies for the treatment of COPD have lagged. Here, we review the molecular approaches that have the potential for developing novel therapies for COPD.
Phaseolus coccineus Seed: A Valued Resource for Bioactive Compounds Targeting Health and Tumor Cells
Authors: Russo Rita , Colantuono Antonio , Di Gaetano Sonia , Capasso Domenica , Tito Annalisa , Pedone Emilia , Pirone Luciano
Published: February 2025

Human galectin-3 (Gal-3), a β-galactoside binding lectin through its Carbohydrate Recognition Domain (CRD), is implicated in a wide range of cellular functions and is involved in critical biological processes including pathogen recognition, immune response, inflammation and fibrosis. Recently, Gal-3 has gained increasing attention for its role in pathological conditions such as cancer, where it influences cancer growth and progression, inflammatory processes and oxidative stress, opening the search for potential inhibitors. In this context, several naturally derived molecules have attracted particular interest, some of them being used in clinical trials. Here, we used the seeds of the legume Phaseolus coccineus as a green resource for bioactive compounds. The peptide-rich crude extracts were chemically characterized for their peptide and polyphenol contents, as well as their in vitro antioxidant activity, and the powerful obtained extract was tested for biological activities such as cytotoxicity and antioxidant and anti-inflammatory effects on cellular models. Furthermore, the interaction between the crude extract and the CRD of recombinant Gal-3 was verified with the aim of associating its biological effects with the inhibition of Gal-3 activity.
A Review of FDA-Approved Multi-Target Angiogenesis Drugs for Brain Tumor Therapy
Authors: Buzatu Iuliana Mihaela , Tataranu Ligia Gabriela , Duta Carmen , Stoian Irina , Alexandru Oana , Dricu Anica
Published: February 2025

Neovascularization is an important process in brain tumor development, invasion and metastasis. Several research studies have indicated that the VEGF signaling target has potential for reducing angiogenesis in brain tumors. However, targeting VEGF signaling has not met the expected efficacy, despite initial enthusiasm. This is partly because tumors cleverly use alternative growth factor pathways, other than VEGF signaling, to restore angiogenesis. Multi-target inhibitors have been developed to inhibit several receptor kinases that play a role in the development of angiogenesis. By simultaneously affecting various receptor kinases, these treatments can potentially obstruct various angiogenic pathways that are involved in brain cancer advancement, often offering a more holistic strategy than treatments focusing on just one kinase. Since 2009, the FDA has approved a number of multi-kinase inhibitors that target angiogenic growth factor receptors (e.g., VEGFR, PDGFR, FGFR, RET, c-KIT, MET, AXL and others) for treatment of malignant diseases, including brain cancer. Here, we present some recent results from the literature regarding the preclinical and clinical effects of these inhibitors on brain tumors.
Dinaciclib Interrupts Cell Cycle and Induces Apoptosis in Oral Squamous Cell Carcinoma: Mechanistic Insights and Therapeutic Potential
Authors: Oner Muhammet , Cheng Yu-Chiao , Soong Shiuan-Woei , Cheng Pang-Ting , Wang Yan-Hsiung , Yang Shun-Fa , Tsai Stella Chin-Shaw , Lin Ho
Published: February 2025

Dinaciclib, a potent cyclin-dependent kinase (CDK) inhibitor, has demonstrated considerable antitumor effects in various malignancies. However, its impact on oral squamous cell carcinoma (OSCC), a predominant and highly aggressive form of head and neck squamous cell carcinoma (HNSC) with limited treatment options, remains underexplored. We conducted gene set enrichment analyses in HNSC patients that reinforced the relevance of these cell cycle-related genes to OSCC pathogenesis. Given the known dysregulation of cell cycle-related genes in HNSC patients, we hypothesized that Dinaciclib may inhibit OSCC growth by targeting overexpressed cyclins and CDKs, thereby disrupting cell cycle progression and inducing apoptosis. This study investigated Dinaciclib’s effects on cell proliferation, cell cycle progression, and apoptosis in the OSCC cell lines Ca9-22, OECM-1, and HSC-3. Our results demonstrated that Dinaciclib significantly reduces OSCC cell proliferation in a dose-dependent manner. Flow cytometry and Western blot analyses showed that Dinaciclib induces cell cycle arrest at the G1/S and G2/M transitions by downregulating Cyclins A, B, D, and E, along with CDKs 1 and 2—key regulators of these checkpoints. Furthermore, Dinaciclib treatment upregulated apoptotic markers, such as cleaved-caspase-3 and cleaved-PARP, confirming its pro-apoptotic effects. In conclusion, these findings highlight Dinaciclib’s therapeutic promise in OSCC by simultaneously disrupting cell cycle progression and inducing apoptosis. These results support further exploration of Dinaciclib as a viable monotherapy or combination treatment in OSCC and other HNSC subtypes to improve patient outcomes.
Maternal Hyperandrogenemia and the Long-Term Neuropsychological, Sex Developmental, and Metabolic Effects on Offspring
Authors: Darlas Menelaos , Kalantaridou Sophia , Valsamakis Georgios
Published: February 2025

Maternal hormonal and metabolic disorders, such as diabetes and obesity, can adversely affect the intrauterine environment, resulting in suboptimal fetal growth and an elevated risk of cardiovascular and metabolic diseases in the later life of the offspring. In this review, we examine the long-term impact of elevated maternal androgen levels during pregnancy on offspring. Maternal hyperandrogenemia is linked to various neurodevelopmental disorders, including attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety-like behaviors, mediated by alterations in key brain regions responsible for emotion and cognition. Furthermore, children born to mothers with hyperandrogenemia exhibit heightened risk of metabolic and cardiovascular dysfunctions, such as obesity, insulin resistance, and hypertension, which can manifest early in life. Prenatal exposure to androgens has also been linked to reduced birth weights and altered fetal growth, potentially due to impaired placental function. Additionally, maternal testosterone levels influence offspring sex ratios, often favoring male births, though exceptions occur in certain conditions, such as congenital adrenal hyperplasia. The findings of this review underscore the need for healthcare professionals to monitor maternal serum androgen profiles during pregnancy. Further research is needed to determine underlying mechanisms and potential interventions to mitigate these risks.
Strain-Specific Features of Primary Metabolome Characteristic for Extremotolerant/Extremophilic Cyanobacteria Under Long-Term Storage
Authors: Bilova Tatiana , Golushko Nikita , Frolova Nadezhda , Soboleva Alena , Silinskaia Svetlana , Khakulova Anna , Orlova Anastasia , Sinetova Maria , Los Dmitry , Frolov Andrej
Published: February 2025

Cyanobacteria isolated from extreme habitats are promising in biotechnology due to their high adaptability to unfavorable environments and their specific natural products. Therefore, these organisms are stored under a reduced light supply in multiple collections worldwide. However, it remains unclear whether these strains maintain constitutively expressed primary metabolome features associated with their unique adaptations. To address this question, a comparative analysis of primary metabolomes of twelve cyanobacterial strains from diverse extreme habitats was performed by a combined GC-MS/LC-MS approach. The results revealed that all these cyanobacterial strains exhibited clear differences in their patterns of primary metabolites. These metabolic differences were more pronounced for the strains originating from ecologically different extreme environments. Extremotolerant terrestrial and freshwater strains contained lower strain-specifically accumulated primary metabolites than extremophilic species from habitats with high salinity and alkalinity. The latter group of strains was highly diverse in amounts of specific primary metabolites. This might indicate essentially different molecular mechanisms and metabolic pathways behind the survival of the microorganisms in saline and alkaline environments. The identified strain-specific metabolites are discussed with respect to the metabolic processes that might impact maintaining the viability of cyanobacteria during their storage and indicate unique adaptations formed in their original extreme habitats.
1-Pyrene Carboxylic Acid: An Internalization Enhancer for Short Oligoarginines
Authors: Bató Csaba , Szabó Ildikó , Yousef Mo’ath , Lenzinger Dorina , Grébecz Fülöp Károly , Visnovitz Tamás , Bősze Szilvia E. , Bánóczi Zoltán , Mező Gábor
Published: February 2025

Getting through the cell membrane is challenging, and transporting a therapeutic agent while entering the cell is even more complicated. Cell-penetrating peptides (CPPs) are valuable tools for solving this problem, although they have drawbacks. In this work, the synthesis and investigation of efficient CPPs are described. We used an aromatic group, 1-pyrene carboxylic acid (PCA), to enhance internalization. We designed oligoarginines to investigate the effect of PCA in different positions at the N-terminus or in the side chain. Our novel peptide derivatives showed remarkable internalization on tumor cell lines, and more than one endocytic pathway plays a role in their internalization mechanism. With this modification, there is an opportunity to design short oligoarginines that can rival well-known CPPs like octaarginine in internalization.
Targeting Tumor Microenvironment Interactions in Chronic Lymphocytic Leukemia Using Leukotriene Inhibitors
Authors: Sadeghi Laia , Merrien Magali , Björkholm Magnus , Österborg Anders , Sander Birgitta , Claesson Hans-Erik , Wright Anthony P. H.
Published: February 2025

Chronic lymphocytic leukemia (CLL) cells depend on microenvironment niches for proliferation and survival. The adhesion of tumor cells to stromal cells in such niches triggers the activation of signaling pathways crucial for their survival, including B-cell receptor (BCR) signaling. While inhibitors of Bruton’s tyrosine kinase (BTKi) have shown efficacy in patients with CLL by disrupting these interactions, acquired resistance and toxicity remain a challenge during long-term therapy. Thus, identifying additional therapeutic modalities is important. Previously, we demonstrated that 5-lipoxygenase (5-LOX) pathway inhibitors reduced mantle cell lymphoma (MCL) cell adhesion to stromal cells, motivating us to investigate their potential in the context of CLL. We employed an ex vivo co-culture model to study CLL cell adhesion to stromal cells in the absence and presence of 5-LOX pathway inhibitors (zileuton and MK886) as well as the BTKi ibrutinib that was included for comparative purposes. Our findings demonstrated that different CLL samples adhere to stromal cells differentially. We observed a variable decrease in CLL cell adhesion to stromal cells following the inhibition of the 5-LOX pathway across a spectrum of patient samples that was distinct to the spectrum for ibrutinib. Positive and negative correlations were shown between the clinical and genetic features of the CLL samples and their level of adherence to stromal cells in both the absence and presence of the tested inhibitors. These results suggest the 5-LOX pathway as a candidate for assessment as a new therapeutic target in CLL.
Base-Labile Safety-Catch Linker: Synthesis and Applications in Solid-Phase Peptide Synthesis
Authors: Noki Sikabwe , Saneii Hossain , Torre Beatriz G. de la , Albericio Fernando
Published: February 2025

The safety-catch concept involves a protecting group that remains stable under a range of chemical conditions and subsequently becomes labile under one of those conditions upon a chemical modification of the protecting group. The safety-catch approach introduces flexibility into the scheme, enabling the use of the same reagent in two distinct steps of the chemical process. For example, it facilitates α-amino deprotection and final cleavage in a solid-phase peptide synthesis scheme. Herein, we developed a safety-catch linker based on sulfinyl designed to enable peptide elongation via fluorenylmethoxycarbonyl (Fmoc) chemistry. Subsequently, upon chemical modification (oxidation of the sulfinyl group into the corresponding sulfone), the peptide is released using a secondary amine via a -elimination reaction, which also serves to remove the Fmoc group in each step. The optimization of both key reactions, oxidation of the linker, and peptide release were achieved using a multi-detachable system, which allows specific control of both reactions. The use of this linker opens the possibility of cleaving peptides from the solid support without trifluoroacetic acid.
Isolation, Characterization, and In Vitro Cell Studies of Plant-Based Exosome-like Nanovesicles for Treatment of Early Osteoarthritis
Authors: Rashidi Narjes , Liu Chaozong , Guillot Pascale V. , Tamaddon Maryam
Published: February 2025

Osteoarthritis, affecting over 8 million people in the UK, remains a debilitating condition with limited treatment options. Current therapies primarily address symptoms and can exacerbate joint damage over time. Developing disease-modifying drugs that alleviate inflammation and promote joint regeneration is crucial for long-term patient benefit. This study investigates the potential of exosome-like nano-vesicles isolated from grapefruit juice (GEVs) as a novel therapeutic approach for osteoarthritis. GEVs possess regenerative properties and present a promising avenue for clinical translation. In this study, nano-vesicles were isolated and characterized in terms of protein quantification, size, and morphology. In vitro studies demonstrated the safety and efficacy of GEVs, showing an enhancement in human chondrocyte migratory activity of over 13%. GEVs exhibited a dual mechanism of action, reducing inflammation and oxidative stress while promoting cellular regeneration. Specifically, they reduced the expression of COX2 and PTGS2, markers associated with inflammation and pain sensitization, and enhanced the expression of antioxidant genes SD2 and GPX in osteoarthritic-like chondrocytes. Additionally, GEVs downregulated the expression of ADAMTS-5 and hypertrophic COL10 while upregulating chondrogenic markers ACAN, COL2, and SOX9. This research signifies a significant advancement in osteoarthritis therapy, offering a natural, safe, and cost-effective treatment option with the potential for long-lasting benefits. Clinical translation of GEV therapy holds promise for improving patient outcomes and reducing the burden on healthcare systems.