bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Outcomes and Associated Morbidity of Active and Expectant Management of Second-Trimester Placenta Accreta Spectrum (PAS)
Authors: Munoz Jessian L. , Counts Rachel , Lacue Amanda E. , Ireland Kayla E. , Ramsey Patrick S. , Brandi Kristyn
Published: January 2025

Background and Objectives: Management of second-trimester placenta accreta spectrum (PAS) is currently center-dependent with minimal evidence-based practices. This study aims to analyze outcomes of hysterectomy as second-trimester active management (AM) versus cesarean hysterectomy as expectant management (EM) in cases of PAS with intraoperative and postoperative outcomes. Materials and Methods: This study is a retrospective case-control study of patients with a pathology-confirmed diagnosis of PAS managed at a single center over 16 years (2005–2020). All cases were diagnosed during the first or second trimester by ultrasonography and managed by the same multidisciplinary team with delivery within the second trimester. Results: Thirty-four patients with PAS were diagnosed and delivered by the second trimester. Of these, (41.1%) elected for active management and 20 (58.9%) for expectant management but ultimately required delivery prior to 28 weeks’ gestation. Baseline demographics were similar between groups. Intraoperatively, no differences were noted in operative time (191.5 vs. 203 min, p = 0.85), blood loss (2300 vs. 2600 cc, p = 0.85), or incidental cystotomy (1 vs. 7, p = 0.10). Postoperative length of stay was similar (3 vs. 3.5 days, p = 0.28), and ICU admission was not statistically different (6 vs. 12, p = 0.48). Conclusions: This retrospective study suggests that when hysterectomy is planned, there is no difference in maternal outcomes and morbidity with an expectant management with cesarean hysterectomy in the second trimester compared to proactive cesarean hysterectomy.
Chitosan’s Ability to Remove the Smear Layer—A Systematic Review of Ex Vivo Studies
Authors: Ferreira-Reguera Ana , Ferreira Inês , Pina-Vaz Irene , Martín-Biedma Benjamín , Martín-Cruces José
Published: January 2025

Background and Objectives: This systematic review aimed to compare the effect of chitosan in smear layer removal with other commonly used chelators during root canal treatment. Materials and Methods: The PRISMA guidelines were followed. Ex vivo studies performed in non-endodontically treated extracted human permanent teeth with a fully formed apex, in which sodium hypochlorite was the main irrigant and chitosan was used as final irrigation to observe its capacity to remove the smear layer using a Scanning Electron Microscope (SEM), were included. In addition, reviews, letters, opinion articles, conference abstracts, book chapters, or articles that did not use a control group were excluded. A literature search was undertaken without limits on time or language, until February 2024, in PubMed—MEDLINE, Scopus, Web of Science, and in the electronic archives of four endodontic journals. The risk of bias was evaluated by adapting the risk of bias assessment used in a previous study. Study selection, data collection, and synthesis were performed and the risk of bias was assessed by two independent reviewers. Results: Six studies fulfilled the eligibility criteria and were included. Four studies found chitosan to be as effective as EDTA and one paper showed it was more effective than EDTA and MTAD; however, one article found it to be comparable to citric acid. The overall risk of bias was medium. Quantitative analysis of the results was not possible due to the heterogeneity found between the study methodologies of the included articles. Conclusions: Within the limitations of this study, 0.2% chitosan may be considered as a promising irrigation solution when employed as a final irrigant in order to remove the smear layer. Nonetheless, a standardized protocol for the use of chelators in root canal treatment should be established in future studies.
Are Suggested Hiking Times Accurate? A Validation of Hiking Time Estimations for Preventive Measures in Mountains
Authors: Vecchiato Marco , Borasio Nicola , Scettri Emiliano , Franzoi Vanessa , Duregon Federica , Savino Sandro , Ermolao Andrea , Neunhaeuserer Daniel
Published: January 2025

Background and Objectives: Accurate hiking time estimate is crucial for outdoor activity planning, especially in mountainous terrains. Traditional mountain signage and online platforms provide generalized hiking time recommendations, often lacking personalization. This study aims to evaluate the variability in hiking time estimates from different methods and assess the potential of a novel algorithm, MOVE, to enhance accuracy and safety. Materials and Methods: A cross-sectional analysis was conducted using data from 25 Italian loop trails selected via the Wikiloc platform, considering user-uploaded GPS data from at least 20 users per trail. Real-world hiking times were compared with estimations from Komoot, Outdooractive, mountain signage, and the MOVE algorithm, which incorporates individualized biological and trail characteristics. Results: Significant discrepancies were observed between actual hiking times and estimates from Komoot (ΔWK: −48.92 ± 57.16 min), Outdooractive (ΔWO: −69.13 ± 58.23 min), and mountain signage (ΔWS: −29.59 ± 59.90 min; all p < 0.001). In contrast, MOVE showed no statistically significant difference (ΔWM: −0.27 ± 65.72 min; p = 0.278), providing the most accurate predictions. Conclusions: Current hiking time estimation methods show substantial variability and inaccuracy, which may pose safety risks. MOVE demonstrated superior accuracy, offering personalized hiking time predictions based on user-specific data and trail characteristics. Integrating such advanced tools into outdoor activity planning could enhance safety and accessibility, particularly for individuals with chronic conditions. Further studies should explore integrating real-time health data to refine these tools.
Awareness and Implementation of Sports Injury Prevention Programs Among Physical Therapists in Saudi Arabia: A Cross-Sectional Study
Authors: Alnefaie Yousef M. , Seyam Mohamed K. , Alzhrani Msaad , Alanazi Ahmad , Alzahrani Faris S. , Alsaadoon Saud M. , Hasan Shahnaz
Published: January 2025

Background and Objectives: Sports injury prevention programs (SIPPs) are crucial for mitigating sports injuries and enhancing athletes’ performance. In Saudi Arabia, the sports sector is growing, and the awareness and implementation of sports injury prevention programs (SIPPs) among physical therapists require examination. This study aims to evaluate physiotherapists’ awareness of and the implementation of sports injury prevention programs (SIPPs) in the Saudi Arabian region with findings that could enhance rehabilitation and sports injury prevention practices. Materials and Methods: A self-administered online questionnaire was distributed to licensed physiotherapists in Saudi Arabia. Three hundred sixty-six participants responded to the questionnaire, of whom 55.5% were male and 44.5% were female physiotherapists. Results: Licensed physical therapists show a high awareness of sports injury prevention, with 83.9% agreeing or strongly agreeing. However, only 53.8% were aware of sports injury prevention programs, and 37.7% reported actively implementing them. Sports physical therapists scored significantly higher in awareness and implementation than other specialties (p < 0.001) with no significant regional differences. Educational qualification was also significant, with those holding a master’s degree or higher reporting greater awareness and implementation than those with a bachelor’s degree (p = 0.007). There was a strong positive correlation between awareness and implementation (r = 0.723, p < 0.01), along with weak correlations between awareness and perceived barriers (r = 0.270, p < 0.01) and implementation and barriers (r = 0.280, p < 0.01). Conclusions: This study finds that physical therapists in Saudi Arabia have moderate-to-low awareness and implementation of sports injury prevention programs (SIPPs), especially outside of sports-specific fields. Sports physical therapists and those with higher education have significant awareness. There are minimal regional differences but a strong positive correlation between awareness and implementation. Enhanced training, resources, and institutional support are needed to improve SIPP implementation in rehabilitation.
Intracellular Membrane Contact Sites in Skeletal Muscle Cells
Authors: Serano Matteo , Perni Stefano , Pierantozzi Enrico , Laurino Annunziatina , Sorrentino Vincenzo , Rossi Daniela
Published: January 2025

Intracellular organelles are common to eukaryotic cells and provide physical support for the assembly of specialized compartments. In skeletal muscle fibers, the largest intracellular organelle is the sarcoplasmic reticulum, a specialized form of the endoplasmic reticulum primarily devoted to Ca2+ storage and release for muscle contraction. Occupying about 10% of the total cell volume, the sarcoplasmic reticulum forms multiple membrane contact sites, some of which are unique to skeletal muscle. These contact sites primarily involve the plasma membrane; among these, specialized membrane contact sites between the transverse tubules and the terminal cisternae of the sarcoplasmic reticulum form triads. Triads are skeletal muscle-specific contact sites where Ca2+ channels and regulatory proteins assemble to form the so-called calcium release complex. Additionally, the sarcoplasmic reticulum contacts mitochondria to enable a more precise regulation of Ca2+ homeostasis and energy metabolism. The sarcoplasmic reticulum and the plasma membrane also undergo dynamic remodeling to allow Ca2+ entry from the extracellular space and replenish the stores. This process involves the formation of dynamic membrane contact sites called Ca2+ Entry Units. This review explores the key processes in biogenesis and assembly of intracellular membrane contact sites as well as the membrane remodeling that occurs in response to muscle fatigue.
MetaboLabPy—An Open-Source Software Package for Metabolomics NMR Data Processing and Metabolic Tracer Data Analysis
Authors: Ludwig Christian
Published: January 2025

Introduction: NMR spectroscopy is a powerful technique for studying metabolism, either in metabolomics settings or through tracing with stable isotope-enriched metabolic precursors. MetaboLabPy (version 0.9.66) is a free and open-source software package used to process 1D- and 2D-NMR spectra. The software implements a complete workflow for NMR data pre-processing to prepare a series of 1D-NMR spectra for multi-variate statistical data analysis. This includes a choice of algorithms for automated phase correction, segmental alignment, spectral scaling, variance stabilisation, export to various software platforms, and analysis of metabolic tracing data. The software has an integrated help system with tutorials that demonstrate standard workflows and explain the capabilities of MetaboLabPy. Materials and Methods: The software is implemented in Python and uses numerous Python toolboxes, such as numpy, scipy, pandas, etc. The software is implemented in three different packages: metabolabpy, qtmetabolabpy, and metabolabpytools. The metabolabpy package contains classes to handle NMR data and all the numerical routines necessary to process and pre-process 1D NMR data and perform multiplet analysis on 2D-1H, 13C HSQC NMR data. The qtmetabolabpy package contains routines related to the graphical user interface. Results: PySide6 is used to produce a modern and user-friendly graphical user interface. The metabolabpytools package contains routines which are not specific to just handling NMR data, for example, routines to derive isotopomer distributions from the combination of NMR multiplet and GC-MS data. A deep-learning approach for the latter is currently under development. MetaboLabPy is available via the Python Package Index or via GitHub.
A Comprehensive Review on Bio-Based Polybenzoxazines Emphasizing Their Antimicrobial Property
Authors: Asrafali Shakila Parveen , Periyasamy Thirukumaran , Lee Jaewoong
Published: January 2025

Polybenzoxazines (PBzs), a class of high-performance thermosetting polymers, have gained significant attention for their exceptional thermal stability, mechanical properties, and chemical resistance, making them ideal for aerospace, electronics, and biomedical applications. Recent advancements emphasize their antimicrobial potential, attributed to unique structural properties and the ability to incorporate bio-active functional groups. This review highlights the synthesis, antimicrobial mechanisms, and applications of PBzs and their bio-based derivatives, focusing on sustainable materials science. PBzs demonstrate antimicrobial efficacy through mechanisms such as hydrophobic surface interactions and reactive functional group formation, preventing microbial adhesion and biofilm development. The incorporation of functional groups like amines, quaternary ammonium salts, and phenolic moieties disrupts microbial processes, enhancing antimicrobial action. Modifications with metal nanoparticles, organic agents, or natural bio-actives further augment these properties. Notable bio-based benzoxazines include derivatives synthesized from renewable resources like curcumin, vanillin, and eugenol, which exhibit substantial antimicrobial activity and environmental friendliness. Hybrid PBzs, combining natural polymers like chitosan or cellulose, have shown improved antimicrobial properties and mechanical performance. For instance, chitosan-PBz composites significantly inhibit microbial growth, while cellulose blends enhance film-forming capabilities and thermal stability. PBz nanocomposites, incorporating materials like silver nanoparticles, present advanced applications in biomedical and marine industries. Examples include zirconia-reinforced composites for dental restoration and urushiol-based PBzs for eco-friendly antifouling solutions. The ability to customize PBz properties through molecular design, combined with their inherent advantages such as flame retardancy, low water absorption, and excellent mechanical strength, positions them as versatile materials for diverse industrial and medical applications. This comprehensive review underscores the transformative potential of PBzs in addressing global challenges in antimicrobial material science, offering sustainable and multifunctional solutions for advanced applications.
Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention
Authors: Wang Xiaohua , Deng Xiaofei , Xin Lilan , Dong Chune , Hu Guoyuan , Zhou Hai-Bing
Published: January 2025

In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system’s applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach. A novel esterase-activated EPR strategy prodrug, OBHSA-PEG-DCM, was designed. This prodrug links OBHSA, a protein degrader capable of efficient ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4H-pyran, DCM) via an ester bond. This integration facilitates targeted drug delivery and enhances the retention of the fluorescent group within the tumor, allowing distinct in vivo tumor imaging periods. Experimental results show that, benefiting from overexpressed esterase in cancer cells, OBHSA-PEG-DCM can be efficiently hydrolyzed, releasing OBHSA and pegylated DCM. OBHSA demonstrated potent inhibition against MCF-7 cells (IC50 = 1.09 μM). Simultaneously, pegylated DCM exhibited remarkable in vivo imaging capabilities, lasting up to 12 days in mice, due to the enhanced permeability and retention (EPR) effect. OBHSA-PEG-DCM holds promise as a theranostic agent for ERα-positive breast cancer, offering both therapeutic and diagnostic capabilities. Importantly, this study highlights the utility of pegylated NIR fluorophores for long-circulating drug delivery systems, addressing current challenges in achieving high-contrast tumor imaging and effective targeted drug release.
NMR and MD Simulations of Non-Ionic Surfactants
Authors: Buntkowsky Gerd , Hoffmann Markus
Published: January 2025

Non-ionic surfactants are an important solvent in the field of green chemistry with tremendous application potential. Understanding their phase properties in bulk or in confined environments is of high commercial value. In recent years, the combination of molecular dynamics (MD) simulations with multinuclear solid-state NMR spectroscopy and calorimetric techniques has evolved into the most powerful tool for their investigation. Showing recent examples from our groups, the present review demonstrates the power and versatility of this approach, which can handle both small model-surfactants like octanol and large technical surfactants like technical polyethylene glycol (PEG) mixtures and reveals otherwise unobtainable knowledge about their phase behavior and the underlying molecular arrangements.
Large-Scale Compatible Roll-to-Roll Coating of Paper Electrodes and Their Compatibility as Lithium-Ion Battery Anodes
Authors: Blomquist Nicklas , Phadatare Manisha , Patil Rohan , Zhang Renyun , Leuschen Noah , Hummelgård Magnus
Published: January 2025

A recyclability perspective is essential in the sustainable development of energy storage devices, such as lithium-ion batteries (LIBs), but the development of LIBs prioritizes battery capacity and energy density over recyclability, and hence, the recycling methods are complex and the recycling rate is low compared to other technologies. To improve this situation, the underlying battery design must be changed and the material choices need to be made with a sustainable mindset. A suitable and effective approach is to utilize bio-materials, such as paper and electrode composites made from graphite and cellulose, and adopt already existing recycling methods connected to the paper industry. To address this, we have developed a concept for fabricating fully disposable and resource-efficient paper-based electrodes with a large-scale roll-to-roll coating operation in which the conductive material is a nanographite and microcrystalline cellulose mixture coated on a paper separator. The overall best result was achieved with coated roll 08 with a coat weight of 12.83(22) g/m2 and after calendering, the highest density of 1.117(97) g/cm3, as well as the highest electrical conductivity with a resistivity of 0.1293(17) mΩ·m. We also verified the use of this concept as an anode in LIB half-cell coin cells, showing a specific capacity of 147 mAh/g, i.e., 40% of graphite’s theoretical performance, and a good long-term stability of battery capacity over extended cycling. This concept highlights the potential of using paper as a separator and strengthens the outlook of a new design concept wherein paper can both act as a separator and a substrate for coating the anode material.
Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
Authors: Coradduzza Donatella , Cruciani Sara , Di Lorenzo Biagio , De Miglio Maria Rosaria , Zinellu Angelo , Maioli Margherita , Medici Serenella , Erre Gian Luca , Carru Ciriaco
Published: January 2025

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective role in endothelial function. However, the relationship between Humanin levels and ED in RA, as well as the interaction between Humanin and non-coding RNAs such as Long Non-Coding RNA GAS5, microRNA-21 (miR-21), and microRNA-103 (miR-103), remains unclear. Objective: This study aimed to investigate the relationship between circulating Humanin levels, non-coding RNAs (GAS5, miR-21, miR-103), and endothelial dysfunction (ED) in patients with RA. Additionally, we explored the correlation between Humanin expression and specific non-coding RNAs (GAS5, miR-21, and miR-103) to better understand their potential role in vascular health. Methods: Peripheral ED was assessed using flow-mediated pulse amplitude tonometry, with Ln-RHI values <0.51 indicating dysfunction. Humanin levels, GAS5, miR-21, and miR-103 were measured in RA patients. Univariate and multivariate analyses were conducted to determine the relationship between these biomarkers and ED. Kaplan–Meier survival analysis and ROC curve analysis were used to assess the prognostic value of Humanin. Results: Higher Humanin levels were significantly associated with better endothelial function (OR = 0.9774, p = 0.0196). Kaplan–Meier analysis demonstrated that higher Humanin levels correlated with improved survival (p < 0.0001). The non-coding RNAs (GAS5, miR-21, and miR-103) did not show significant associations with ED. Conclusions: Humanin is a potential protective biomarker for endothelial dysfunction and survival in RA patients. Further research is needed to explore the interaction between Humanin and non-coding RNAs in the context of vascular health.
Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines
Authors: Grant William , Wimalawansa Sunil , Pludowski Pawel , Cheng Richard
Published: January 2025

Vitamin D offers numerous under-recognized health benefits beyond its well-known role in musculoskeletal health. It is vital for extra-renal tissues, prenatal health, brain function, immunity, pregnancy, cancer prevention, and cardiovascular health. Existing guidelines issued by governmental and health organizations are bone-centric and largely overlook the abovementioned extra-skeletal benefits and optimal thresholds for vitamin D. In addition, they rely on randomized controlled trials (RCTs), which seldom show benefits due to high baseline 25-hydroxyvitamin D [25(OH)D] concentrations, moderate supplementation doses, and flawed study designs. This review emphasizes the findings from prospective cohort studies showing that higher 25(OH)D concentrations reduce the risks of major diseases and mortality, including pregnancy and birth outcomes. Serum concentrations > 30 ng/mL (75 nmol/L) significantly lower disease and mortality risks compared to <20 ng/mL. With 25% of the U.S. population and 60% of Central Europeans having levels <20 ng/mL, concentrations should be raised above 30 ng/mL. This is achievable through daily supplementation with 2000 IU/day (50 mcg/day) of vitamin D3, which prevent diseases and deaths. Furthermore, a daily dose between 4000 and 6000 IU of vitamin D3 to achieve serum 25(OH)D levels between 40 and 70 ng/mL would provide greater protection against many adverse health outcomes. Future guidelines and recommendations should integrate the findings from observational prospective cohort studies and well-designed RCTs to improve public health and personalized care.
Profiles of 71 Human Milk Oligosaccharides and Novel Sub-Clusters of Type I Milk: Results from the Ulm SPATZ Health Study
Authors: Peng Zhuoxin , Siziba Linda P. , Mank Marko , Stahl Bernd , Gonsalves John , Wernecke Deborah , Rothenbacher Dietrich , Genuneit Jon
Published: January 2025

Background/Objectives: Although approximately 160 human milk oligosaccharides (HMOs) have been identified, current studies on HMO quantitation are limited to the 10–19 most abundant HMOs. We assessed the variations in the relative concentrations of 71 HMO structures over lactation in human milk samples by an advanced liquid chromatography–mass spectrometry approach. Methods: Samples were collected from 64 mothers at 6 weeks, 6 months, and 12 months of lactation in the Ulm SPATZ Health Study, a German birth cohort. In this longitudinal study, we fitted linear mixed-effect models to analyze changes in the log2-transformed and standardized HMO concentration over time. Based on the profile of 71 HMOs, we also fitted a group-based multi-trajectory (GBMT) model to cluster mothers secreting cluster type I milk, who account for the majority of lactating mothers. Results: We found that 52 HMOs had a decreasing trend (regression coefficients ranging from −1.41 to −0.17) and 9 had an increasing trend (regression coefficients ranging from 0.25 to 0.64) during lactation, and the findings were statistically significant after multiple testing corrections. Using human milk samples of 49 mothers with type I milk, we further identified two novel sub-clusters with distinct longitudinal trajectories of concentrations of 71 HMOs during lactation: Type I-a (N = 20) and I-b (N = 29). These sub-clusters were not associated with maternal non-genetic characteristics. Conclusions: Our findings extend existing knowledge about the structural diversity of HMOs and their variations over lactation. These may pave the way to investigate the potential nutritional benefits of various HMOs on infant health and early life development in the future.
The Effects of Heat Stress on the Physiology and Mortality of the Rhizostome Upside-Down Jellyfish Cassiopea xamachana—Observations Throughout the Life Cycle
Authors: Fitt William K. , Hofmann Dietrich K. , Ohdera Aki H. , Kemp Dustin W. , Morandini André C.
Published: January 2025

This study was designed to investigate the impact of heat stress on the physiological changes and mortality rates of different life stages of the rhizostome jellyfish species Cassiopea xamachana, including planula larvae, scyphistomae (polyps), and medusae. Both larval and scyphistoma stages of C. xamachana are relatively tolerant to high temperatures, but both experience nearly 100% mortality at 36 °C. Increasing temperatures also induced stage-specific effects. Settlement rates of artificially induced larvae were near 100% at lower temperatures but decreased at 34–36 °C; larvae were dead at 36 °C. When scyphistomae of C. xamachana were subjected to a gradual increase in temperature from 28 to 38 °C, polyp size declined steadily in starved animals, with animals showing clear signs of temperature stress between 35 and 36 °C. Small medusae of C. xamachana pulsed more than larger medusae and tended to have peak pulse rates at higher temperatures (~35 °C) compared to larger medusae (~29–33 °C), though the latter was not significant. At a temperature of 39 °C, all the medusae exhibited signs of heat stress, including pulsing erratically (generally lower) rather than steady rhythmic pulsations, releasing copious amounts of mucus, and having withdrawn oral arms. Temperature data presented here, and in the literature, show that pulsing C. xamachana medusae exhibit a bell-shaped curve, with temperatures over 38 °C being detrimental and becoming lethal at 40 °C. Based on the findings of this study, it is proposed that the medusa stage of C. xamachana has a higher tolerance for elevated temperatures compared to both the larvae and the polyps. Predictions of global climate change indicate that populations of C. xamachana will likely face longer and hotter summer periods, leading to increased population sizes. However, higher temperatures pose a greater risk to the survival of the species as they increase mortality in the polyp and larval stages compared to the medusa stage.
Lepton Flavour Universality Tests Using Semileptonic b-Hadron Decays at the LHCb Detector
Authors: Kutsenko Bogdan
Published: January 2025

This review highlights advancements in testing Lepton Flavour Universality (LFU) through semileptonic b-hadron decays at the LHCb detector. Measurements of the LFU R(D) and R(D*) provide evidence of deviations from Standard Model (SM) predictions, suggesting the presence of possible New Physics (NP). However, the D★ longitudinal polarisation results are in good agreement with SM expectations, placing constraints on potential NP theories, such as the leptoquarks or charged Higgs models. Further improvements in the measurements’ precision are expected with the new data from LHCb Run 3, collected with higher instantaneous luminosity and improved trigger.
Antibody Responses and the Vaccine Efficacy of Recombinant Glycosyltransferase and Nicastrin Against Schistosoma japonicum
Authors: Dong Bowen , Zhong Haoran , Zhu Danlin , Wu Luobin , Wang Jinming , Li Hao , Jin Yamei
Published: January 2025

Schistosomiasis is a neglected tropical disease and the second most common parasitic disease after malaria. While praziquantel remains the primary treatment, concerns about drug resistance highlight the urgent need for new drugs and effective vaccines to achieve sustainable control. Previous proteomic studies from our group revealed that the expression of Schistosoma japonicum glycosyltransferase and nicastrin as proteins was higher in single-sex males than mated males, suggesting their critical roles in parasite reproduction and their potential as vaccine candidates. In this study, bioinformatic tools were employed to analyze the structural and functional properties of these proteins, including their signal peptide regions, transmembrane domains, tertiary structures, and protein interaction networks. Recombinant forms of glycosyltransferase and nicastrin were expressed and purified, followed by immunization experiments in BALB/c mice. Immunized mice exhibited significantly elevated specific IgG antibody levels after three immunizations compared to adjuvant and PBS controls. Furthermore, immunization with recombinant glycosyltransferase and nicastrin significantly reduced the reproductive capacity of female worms and liver egg burden, though egg hatchability and adult worm survival were unaffected. These findings demonstrate that recombinant glycosyltransferase and nicastrin are immunogenic and reduce female worm fecundity, supporting their potential as vaccine candidates against schistosomiasis.
Plasmid Gene Therapy for Monogenic Disorders: Challenges and Perspectives
Authors: Luís Marco A. , Goes Marcelo A. D. , Santos Fátima Milhano , Mesquita Joana , Tavares-Ratado Paulo , Tomaz Cândida Teixeira
Published: January 2025

Monogenic disorders are a group of human diseases caused by mutations in single genes. While some disease-altering treatments offer relief and slow the progression of certain conditions, the majority of monogenic disorders still lack effective therapies. In recent years, gene therapy has appeared as a promising approach for addressing genetic disorders. However, despite advancements in gene manipulation tools and delivery systems, several challenges remain unresolved, including inefficient delivery, lack of sustained expression, immunogenicity, toxicity, capacity limitations, genomic integration risks, and limited tissue specificity. This review provides an overview of the plasmid-based gene therapy techniques and delivery methods currently employed for monogenic diseases, highlighting the challenges they face and exploring potential strategies to overcome these barriers.
Modelling Hollow Microneedle-Mediated Drug Delivery in Skin Considering Drug Binding
Authors: Bhuimali Tanmoy , Sarifuddin  , Das Diganta Bhusan , Mandal Prashanta Kumar
Published: January 2025

Background/Objectives: Microneedle(MN)-based drug delivery is one of the potential approaches to overcome the limitations of oral and hypodermic needle delivery. An in silico model has been developed for hollow microneedle (HMN)-based drug delivery in the skin and its subsequent absorption in the blood and tissue compartments in the presence of interstitial flow. The drug’s reversible specific saturable binding to its receptors and the kinetics of reversible absorption across the blood and tissue compartments have been taken into account. Methods: The governing equations representing the flow of interstitial fluid, the transport of verapamil in the viable skin and the concentrations in the blood and tissue compartments are solved using combined Marker and Cell and Immersed Boundary Methods to gain a quantitative understanding of the model under consideration. Results: The viscoelastic skin is predicted to impede the transport of verapamil in the viable skin and, hence, reduce the concentrations of all forms in the blood and the tissue compartments. The findings reveal that a higher mean concentration in the viable skin is not always associated with a longer MN length. Simulations also predict that the concentrations of verapamil in the blood and bound verapamil in the tissue compartment rise with decreasing tip diameters. In contrast, the concentration of free verapamil in the tissue increases with increasing injection velocities. Conclusions: The novelty of this study includes verapamil metabolism in two-dimensional viscoelastic irregular viable skin and the nonlinear, specific, saturable, and reversible binding of verapamil in the tissue compartment. The tip diameter and the drug’s injection velocity are thought to serve as regulatory parameters for the effectiveness and efficacy of MN-mediated therapy if the MN is robust enough to sustain the force needed to penetrate a wider tip into the skin.
Redox-Modulating Capacity and Effect of Ethyl Acetate Roots and Aerial Parts Extracts from Geum urbanum L. on the Phenotype Inhibition of the Pseudomonas aeruginosa Las/RhI Quorum Sensing System
Authors: Dimitrova Lyudmila , Mileva Milka , Georgieva Almira , Tzvetanova Elina , Popova Milena , Bankova Vassya , Najdenski Hristo
Published: January 2025

Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections of the urinary tract, upper respiratory tract, gastrointestinal tract, central nervous system, etc. It is possible to develop bacteremia and sepsis in immunocompromised patients. A major problem in treatment is the development of antibiotic resistance. Therefore, new preparations of natural origin are sought, such as plant extracts, which are phytocomplexes and to which it is practically impossible to develop resistance. Geum urbanum L. (Rosacea) is a perennial herb known for many biological properties. This study aimed to investigate the redox-modulating capacity and effect of ethyl acetate (EtOAc) extracts from roots (EtOAcR) and aerial parts (EtOAcAP) of the Bulgarian plant on the phenotype inhibition of the P. aeruginosa Las/RhI quorum sensing (QS) system, which primarily determines drug resistance in pathogenic bacteria, including biofilm formation, motility, and pigment production. We performed QS assays to account for the effects of the two EtOAc extracts. At sub-minimal inhibitory concentrations (sub-MICs) ranging from 1.56 to 6.25 mg/mL, the biofilm formation was inhibited 85% and 84% by EtOAcR and 62% and 39% by EtOAcAP extracts, respectively. At the same sub-MICs, the pyocyanin synthesis was inhibited by 17–27% after treatment with EtOAcAP and 26–30% with EtOAcR extracts. The motility was fully inhibited at 3.12 mg/mL and 6.25 mg/mL (sub-MICs). We investigated the inhibitory potential of lasI, lasR, rhiI, and rhiR gene expression in biofilm and pyocyanin probes with the PCR method. Interestingly, the genes were inhibited by two extracts at 3.12 mg/mL and 6.25 mg/mL. Antiradical studies, assessed by DPPH, CUPRAC, and ABTS radical scavenging methods and superoxide anion inhibition showed that EtOAcAP extract has effective antioxidant capacity. These results could help in the development of new phytocomplexes that could be applied as biocontrol agents to inhibit the phenotype of the P. aeruginosa QS system and other antibiotic-resistant pathogens.
Application of Biochar-Immobilized Bacillus megaterium for Enhancing Phosphorus Uptake and Growth in Rice
Authors: Yu Keru , Wang Zhenyu , Yang Wenyan , Li Shuai , Wu Dongtao , Zheng Hongtao , Ye Zhengqian , Yang Shaona , Liu Dan
Published: January 2025

Phosphorus (P) is an essential nutrient for rice growth, and the presence of phosphate-solubilizing bacteria (PSB) is an effective means to increase soil P content. However, the direct application of PSB may have minimal significance due to their low survival in soil. Biochar serves as a carrier that enhances microbial survival, and its porous structure and surface characteristics ensure the adsorption of Bacillus megaterium. Inoculating rice husk biochar-immobilized with Bacillus megaterium (BMB) resulted in dissolved inorganic and organic P levels of 39.55 and 31.97 mL L−1, respectively. Subsequently, rice pot experiments were conducted to investigate the response of soil microbial P mobilization and P uptake in rice to fertilizer inputs. The organic fertilizer (OF) combined with BMB treatment (MOF) showed the highest soil available phosphorus (AP) at 38 days, with a value of 7.83 mg kg−1, as well as increased the pqqC abundance while decreasing the abundance of phoD bacterial communities compared with the control. Furthermore, the bioavailable P reservoir (H2O–Pi and NaHCO3–Pi) in soil was greatly increased through the fertilizer input and microbial turnover, with the highest H2O–Pi (3.66 mg kg−1) in OF treatment and the highest NaHCO3–Pi (52.65 mg kg−1) in MOF treatment. Additionally, carbon utilization analysis was applied using the commercial Biolog system, revealing that the MOF treatment significantly increased the utilization of carbohydrates, polymers, and amino acid carbon sources. Moreover, compared to the control, MOF treatment significantly increased the shoot (0.469%) and root P (0.516%) content while promoting root development and thereby supporting rice growth. Our study demonstrates that the MOF treatment displayed higher P levels in both soil and rice plants, providing a theoretical basis for further understanding the role of biochar-based bacterial agents in rice P management.
Modulation of Zn Ion Toxicity in Pisum sativum L. by Phycoremediation
Authors: Karcheva Zornitsa , Georgieva Zhaneta , Anev Svetoslav , Petrova Detelina , Paunov Momchil , Zhiponova Miroslava , Chaneva Ganka
Published: January 2025

Microalgae offer a promising alternative for heavy metal removal, and the search for highly efficient strains is ongoing. This study investigated the potential of two microalgae, Coelastrella sp. BGV (Chlorophyta) and Arthronema africanum Schwabe & Simonsen (Cyanoprokaryota), to bind zinc ions (Zn2⁺) and protect higher plants. Hydroponically grown pea (Pisum sativum L.) seedlings were subjected to ZnSO4 treatment for 7 days in either a nutrient medium (Knop) or a microalgal suspension. The effects of increasing Zn2⁺ concentrations were evaluated through solution parameters, microalgal dry weight, pea growth (height, biomass), and physiological parameters, including leaf gas exchange, chlorophyll content, and normalized difference vegetation index (NDVI). Zinc accumulation in microalgal and plant biomass was also analyzed. The results revealed that microalgae increased pH and oxygen levels in the hydroponic medium while enhancing Zn accumulation in pea roots. At low ZnSO4 concentrations (2–5 mM), microalgal suspensions stimulated pea growth and photosynthetic performance. However, higher ZnSO4 levels (10–15 mM) caused Zn accumulation, leading to nutrient deficiencies and growth suppression in microalgae, which ultimately led to physiological disturbances in peas. Coelastrella sp. BGV exhibited greater tolerance to Zn stress and provided a stronger protective effect when co-cultivated with peas, highlighting its potential for phycoremediation applications.
Functional Characterization of the PoWHY1 Gene from Platycladus orientalis and Its Role in Abiotic Stress Tolerance in Transgenic Arabidopsis thaliana
Authors: Ou Chun , Dong Zhiyu , Zheng Xudong , Cheng Wenhui , Chang Ermei , Yao Xiamei
Published: January 2025

The frequent occurrence of extreme weather conditions in the world has brought many unfavorable factors to plant growth, causing the growth and development of plants to be hindered and even leading to plant death, with abiotic stress hindering the growth and metabolism of plants due to severe uncontrollability. The WHY1 transcription factor plays a critical role in regulating gene expression in plants, influencing chlorophyll biosynthesis, plant growth, and development, as well as responses to environmental stresses. The important role of the PoWHY1 gene in regulating plant growth and adaptation to environmental stress has become a hot research topic. However, the mechanism of the PoWHY1 gene in Platycladus orientalis under abiotic stress is still unclear. Here, the PoWHY1 gene was analyzed bioinformatically using P. orientalis as study material, and the role of the gene against abiotic stress conditions in Arabidopsis thaliana was verified using transgenic technology. It was found that overexpression of PoWHY1 increased seed germination, decreased malondialdehyde accumulation, increased proline content, and delayed the senescence process under salt stress. The expression levels of JAZ1, LOX1, ABI1, and ABI2 were decreased, while the expression levels of RAB18, APX1, GSTF6, and DREB2A were increased, indicating that overexpression of PoWHY1 enhanced the salt stress tolerance of A. thaliana. Furthermore, PoWHY1 overexpression also increased drought tolerance in A. thaliana. From the above results, it can be concluded that maintaining high PoWHY1 expression levels in the leaves of P. orientalis can improve their environmental adaptability. The results provide a scientific basis for understanding the gene function of the PoWHY1 gene of P. orientalis under stress conditions and lay the foundation for further research on the function of the PoWHY1 gene.
A Novel Exopolysaccharide Produced by Sphingomonas sp. MT01 and Its Potential Application in Enhanced Oil Recovery
Authors: Lu Mengting , Lu Xiaoxiao , Tao Weiyi , Lin Junzhang , Li Caifeng , Li Shuang
Published: January 2025

Sphingan is a crucial exopolysaccharide (EPS) produced by Sphingomonas genus bacteria with wide-ranging applications in fields such as food, medicine, and petroleum. In this study, a novel sphingan, named MT gum, was overproduced from the wild-type strain Sphingomonas sp. MT01 at a yield of 25.6 g/L in a 5 L fermenter for 52 h at 35 °C. The MT gum was mainly composed of D-glucose (65.91%) and L-guluronic acid (30.69%), as confirmed by RP-HPLC, with Mw 7.24 × 105 Da. The MT gum exhibited excellent rheology and pseudoplasticity characteristics while maintaining function in high-temperature and high-salinity environments. The viscosity retention rates of MT gum (0.1%, w/v) were 54.06% (80 °C, 50,000 mg/L salinity) and 34.78% (90 °C, 50,000 mg/L salinity), respectively. The apparent viscosity of MT solutions (0.1%, w/v) was much higher than that of welan solutions under the same conditions. The MT gum also had the property of instant dissolution and completely swelled in 40 min. Meanwhile, the MT gum was resistant to 3–10 mg/L Fe2+ in the reservoir conditions, ensuring its application in offshore oil fields. These findings suggested that the biopolymer MT gum produced by the strain MT01 had significant potential in enhanced oil recovery (EOR) of high-temperature and high-salinity oil reservoirs.
High-Yield Production of Polyhydroxybutyrate and Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from Crude Glycerol by a Newly Isolated Burkholderia Species Oh_219
Authors: Oh Suk-Jin , Lim Gaeun , Han Yebin , Kim Wooseong , Joo Hwang-Soo , Kim Yun-Gon , Kim Jae-Seok , Bhatia Shashi Kant , Yang Yung-Hun
Published: January 2025

Crude glycerol (CG), a major biodiesel production by-product, is the focus of ongoing research to convert it into polyhydroxyalkanoate (PHA). However, few bacterial strains are capable of efficiently achieving this conversion. Here, 10 PHA-producing strains were isolated from various media. Among them, Burkholderia sp. Oh_219 exhibited the highest polyhydroxybutyrate (PHB) production from glycerol and was therefore characterized further. Burkholderia sp. Oh_219 demonstrated significant tolerance to major growth inhibitors in CG and metabolized the fatty acids present as impurities in CG. Furthermore, the Oh_219 strain was genetically engineered using phaCBP-M-CPF4 and phaJPa to enable the fatty acid-based production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), a component of CG. The resulting strain produced PHBHHx containing 1.0–1.3 mol% of 3HHx from CG. Further supplementation with capric and lauric acids increased the 3HHx molar fraction to 9.7% and 18%, respectively. In a 5 L fermenter, the Oh_219 strain produced 15.3 g/L PHB from 29.6 g/L biomass using a two-stage fermentation system. This is the highest yield reported for PHA production from glycerol by Burkholderia spp. Additionally, PHB produced from CG had a lower melting point than that from pure glycerol and fructose. Taken together, Burkholderia sp. Oh_219 is a promising new candidate strain for producing PHA from CG.
Study of Adhesion–Cohesive Interactions of Modified Bitumen Compositions
Authors: Dyuryagina Antonina , Degert Alyona , Byzova Yuliya , Ostrovnoy Kirill , Demyanenko Alexandr , Lutsenko Aida , Shirina Tatyana
Published: January 2025

The aim of the work was to study the effect of additive concentration on changes in the adhesive and cohesive strength of bitumen. To evaluate the effectiveness of modifiers in the composition of binary and triple bitumen systems in relation to mineral fillers of two grades, the method of determination of the adhesive efficiency and thermodynamic calculations of adhesion and cohesion work were used. The following compounds were used as additives: AS-2 synthesized from the oil refining waste and AG-4I (waste sealing liquid). Adhesion–cohesion processes in modified bitumen systems are limited by the wetting effect of crushed stone and the intensity of intermolecular forces in the condensed phase of the binder. In the binary compositions, the addition of modifiers into bitumen significantly improves the cohesive strength and adhesive efficiency in relation to crushed stone. The introduction of AS-2 into bitumen compositions with AG-4I increases adhesion efficiency and thermodynamic work of adhesion in relation to the filler surface. The adhesion efficiency and thermodynamic work of adhesion in the “bitumen-AG-4I-AS-2” system reach their maximum at CAG-4I = 3.0 g/dm3 and CAS-2 = 1.5 g/dm3. In these concentration modes, the composition ensures maximum increase in adhesion efficiency (AKS = 65.18%; AKA = 48.11%) and the greatest increase in thermodynamic work of adhesion (WA(KS) = 15.79 mN/m; WA(KA) = 14.13 mN/m).
A Critical Review of the Phenomenon of Inhibiting Asphaltene Precipitation in the Petroleum Industry
Authors: Ahmadi Soroush , Khormali Azizollah , Kazemzadeh Yousef
Published: January 2025

This comprehensive review examines chemical and nano-based methods for asphaltene inhibition in the oil industry, focusing on recent developments and challenges. Asphaltene precipitation and deposition remain significant challenges in oil production, affecting wellbore areas, equipment walls, and surface infrastructure. The review analyzes various chemical inhibition mechanisms and evaluation methods, highlighting the emergence of nanotechnology as a promising solution. Metal oxide nanoparticles, organic nanoparticles, and inorganic nonmetal nanoparticles are discussed as effective inhibitors, with particular attention to their performance in different operational conditions, including CO2 flooding processes. The study reveals that nanoparticles’ effectiveness in asphaltene inhibition is attributed to their large specific surface area, strong adsorption capacity, and unique interaction mechanisms with asphaltene molecules. The review also emphasizes the importance of proper inhibitor selection and concentration optimization, as the effectiveness thereof varies with reservoir conditions and crude oil characteristics. Recent developments in functionalized nanoparticles and their applications in enhanced oil recovery are examined, providing insights into future directions for asphaltene management in the petroleum industry.