bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a National System-Level Intervention: Characterization of Burnout Among Trainees of Saudi Postgraduate Healthcare Professions Programs
Authors: Alomar Saud , Alosaimi Fahad D. , Faden Maher , Alhaider Sami A. , Alsaywid Basim S. , Nakshabandi Ziad , Khamis Nehal
Published: February 2025

Background/Objectives: High levels of burnout among healthcare professionals and trainees represent a global problem with identified profound impacts. The collection of national data for better characterization of this problem can guide more needs-sensitive targeted interventions. We aimed to identify the prevalence of burnout, the associated factors, and their impacts among trainees of Saudi postgraduate healthcare professions training programs. Methods: We conducted an anonymous, cross-sectional survey of 11,500 Saudi Commission for Health Specialties trainees from February to May 2019. The survey included items for socio-demographic data, physical health, and work-related items. We used validated instruments to measure burnout (Maslach Burnout Inventory), stress (Perceived Stress Scale), and depression (Patient Health Questionnaire-9). Results: A total of 6606 postgraduate trainees from different healthcare professions responded (mean age of 28.8 ± 3 years). Fifty-six percent reported burnout symptoms. Burnout was lower among female trainees (aOR, 0.73; 95% CI, 0.65–0.82) and higher in trainees working ≥40 h/week (aOR, 1.19; 95% CI, 1.03–1.37) and doing ≥six on-call shifts/month (aOR, 1.18; 95% CI, 1.03–1.37). Harassment and discrimination increased the risk of burnout by 57% and 60% (aOR = 1.57, 95% CI: 1.36–1.80 and aOR, 1.60; 95% CI, 1.38–1.86), respectively. Burnout trainees had 3.57 adjusted odds to report major depression (95% CI 3.11–4.09), were 1.25 times more likely to report major stress (95% CI 1.36–1.80), and were 1.8 times more likely to complain of sleep disorders (95% CI 1.60–2.04). Conclusion: This study identified several personal and work-related risk factors and impacts of burnout among our postgraduate trainees. The findings were helpful in guiding the expansion of the national Da’em well-being and prevention of burnout program efforts to a targeted system-level intervention.
Atherectomy in the Treatment of Peripheral Arterial Disease—A Case Series to Demonstrate Preferable Indications with Good Outcomes and a Literature Review
Authors: Lizwan Marco , Yap Hao Yun , Ch’ng Jack Kian , Chong Tze Tec , Ng Nick Zhi Peng
Published: February 2025

Background: Endovascular therapy for lower-limb arterial disease is widely performed today. A vast array of sheaths, catheters, wires, balloon types, stents, and tools such as atherectomy, thrombectomy, and lithotripsy devices are now available to achieve the best outcomes in terms of vessel patency and ultimately limb salvage. The use of atherectomy devices, however, has raised some controversies in terms of outcome efficacy, cost effectiveness, and safety profile in various series and studies. Objectively, the types and disease pattern in these studies are also greatly heterogeneous. Methods: Here, we reported three cases which exemplify how these atherectomy devices have served as a valuable tool, especially for patients with complex and heavily calcified lesions. Results: The three cases highlighted scenarios where atherectomy displayed good outcomes, each involving the use of atherectomy devices to treat highly calcified vessels. Conclusions: Despite the concerns with atherectomy devices, we believe that with proper selection, patients will benefit most from their ability to achieve the best outcomes of both vessel patency and limb salvage.
First Report on the Artificial Cultivation Techniques of Buchwaldoboletus xylophilus (Boletales, Boletaceae, Buchwaldoboletus) in Southwest China
Authors: Yang Tianwei , Mu Hongjun , Dai Liming , Liu Jing , Xu Xinjing , Gao Feng , Fang Yiwei , Jian Sipeng , He Mingxia , Zhang Chunxia
Published: February 2025

Buchwaldoboletus xylophilus is an edible bolete species belonging to the family Boletaceae and the genus Buchwaldoboletus. It is found in tropical and subtropical regions, which are known for their rare wild resources. In this study, wild B. xylophilus was isolated and cultured, and its biological characteristics and artificial cultivation techniques were studied. The results show that the optimal carbon source, nitrogen source, and inorganic salt for the mycelium growth of B. xylophilus were maltose, ammonium tartrate, and magnesium sulfate, respectively. The most appropriate temperature was 28 °C, and the pH value was between 5 and 6. The most effective combination was determined via orthogonal experimentation, as follows: dextrose, ammonium nitrate, potassium dihydrogen phosphate, and 28 °C. The results of artificial cultivation in mushroom houses show that the mycelium of B. xylophilus was strong and grew well on the culture medium. The mycelial growth rate was 4.54 mm/d, and the fungus bags were filled about 50 days after inoculation. The primordia formed 9 to 14 days after covering with soil and the fruiting body matured in 6~8 days. The average yield of fresh mushrooms reached 131.07 ± 29.38 g/bag, and the average biological efficiency reached 28.48 ± 6.39%. In this study, artificial cultivation technology in respect of B. xylophilus in mushroom houses is reported for the first time. The fruiting bodies obtained through cultivation were identified using morphological and molecular biological methods. This technology offers benefits such as affordability, a brief cultivation cycle, substantial yields, and superior quality, making it ideal for industrial-scale and extensive cultivation.
The Impact of Levator Muscle Advancement With and Without Upper Blepharoplasty on Dry-Eye Symptoms in Unilateral Ptosis: A Comparative Study
Authors: Vasović Dolika D. , Karamarković Miodrag Lj. , Stojičić Milan , Musić Nikola , Colić Milan , Kalezić Tanja , Vasilijević Jelena , Kovačević Igor , Marjanović Ivan , Jeremić Miroslav , Karamarković Verica , Rašić Dejan M.
Published: February 2025

This study investigates the effects of levator advancement, with and without upper blepharoplasty, on dry-eye symptoms in patients with unilateral ptosis. A total of 92 patients were included, divided into three groups based on surgical intervention: Group A (ptosis correction alone), Group B (ptosis correction with blepharoplasty), and Group C (blepharoplasty alone). Dry-eye parameters were assessed preoperatively and postoperatively at 1, 3, and 6 months using Tear Break-Up Time (TBUT), Schirmer test, corneal and conjunctival staining, and the Ocular Surface Disease Index (OSDI) questionnaire. Our findings indicate that patients in Groups A and B exhibited a temporary increase in dry-eye symptoms, with the most significant effects observed in Group B at the 1- and 3-month follow-ups. By 6 months, dry-eye parameters in all groups returned close to baseline levels, underscoring the reversible nature of these symptoms. This study highlights the importance of preoperative counseling regarding potential temporary dry-eye symptoms, particularly for patients undergoing combined ptosis and blepharoplasty procedures. The results support the safety of these surgical approaches, provided there is appropriate patient monitoring and management to ensure symptom resolution over time.
Flexural and Pseudo-Ductile Performance of Unidirectional and Bidirectional Carbon Fabric-Reinforced Mortar
Authors: Yousef Samy , Kalpokaitė-Dičkuvienė Regina , Subadra Sharath P. , Lukošiūtė Stasė Irena
Published: February 2025

This research aims to study the effect of introducing unidirectional (CFu) and bidirectional (CFb) carbon fabric into cement mortar (CM) on its flexural and pseudo-ductile performances. The experiments were performed on fabric/CM samples with a varying fabric distribution (single, double, and triple layers). The cohesion of fabrics in CM matrices and morphology of the damaged surfaces were examined using an optical microscope, while the flexural response was measured using a universal testing machine. The pseudo-ductile property, in the form of the ductility index (DI), was numerically modelled for CM matrices based on the measured flexural curves using different energy criteria models. Microstructure analysis showed a strong fabric cohesion in the matrices along with the production of more hydration products, which led to a transformation in the linear load–deformation relationship of mortar into the ideal shape of ductile material in the case of CFb/CM. In the case of the CFu/CM samples, two main drop points appeared with a long distance between them. In addition, the flexural load was significantly increased by introducing three layers of each type of fabric to CM, with an improvement of 75% (CFu/CM) and 68% (CFb/CM) compared to neat mortar. Similarly, the deformation till break was improved by 452% (CFu/CM) and 367% (CFb/CM). The DI analysis confirmed these results: the DI performance was improved by up to 140% by embedding. Based on these results, carbon fabric has high potential to enhance the strength and ductility of cementitious matrix.
Comparative Analysis of Perturbation Techniques in LIME for Intrusion Detection Enhancement
Authors: Bacevicius Mantas , Paulauskaite-Taraseviciene Agne , Zokaityte Gintare , Kersys Lukas , Moleikaityte Agne
Published: February 2025

The growing sophistication of cyber threats necessitates robust and interpretable intrusion detection systems (IDS) to safeguard network security. While machine learning models such as Decision Tree (DT), Random Forest (RF), k-Nearest Neighbors (K-NN), and XGBoost demonstrate high effectiveness in detecting malicious activities, their interpretability decreases as their complexity and accuracy increase, posing challenges for critical cybersecurity applications. Local Interpretable Model-agnostic Explanations (LIME) is widely used to address this limitation; however, its reliance on normal distribution for perturbations often fails to capture the non-linear and imbalanced characteristics of datasets like CIC-IDS-2018. To address these challenges, we propose a modified LIME perturbation strategy using Weibull, Gamma, Beta, and Pareto distributions to better capture the characteristics of network traffic data. Our methodology improves the stability of different ML models trained on CIC-IDS datasets, enabling more meaningful and reliable explanations of model predictions. The proposed modifications allow for an increase in explanation fidelity by up to 78% compared to the default Gaussian approach. Pareto-based perturbations provide the best results. Among all distributions tested, Pareto consistently yielded the highest explanation fidelity and stability, particularly for K-NN ( = 0.9971, S = 0.9907) and DT ( = 0.9267, S = 0.9797). This indicates that heavy-tailed distributions fit well with real-world network traffic patterns, reducing the variance in attribute importance explanations and making them more robust.
A Constrained Multi-Objective Optimization Algorithm with a Population State Discrimination Model
Authors: Zhao Shaoyu , Jia Heming , Li Yongchao , Shi Qian
Published: February 2025

The solution to constrained multi-objective optimization problems (CMOPs) requires optimizing the objective functions while satisfying the constraint conditions. To effectively address CMOPs, algorithms must balance objectives and constraints. However, the limited adaptability of specific constraint-handling techniques (CHTs) has hindered the widespread applicability of constrained multi-objective evolutionary algorithms (CMOEAs). To overcome this limitation, this article proposes a population state-based CMOEA. First, a model is developed to identify population states based on the positions of the primary and auxiliary populations. Tailored environmental selection models are then designed for the auxiliary population according to different states, enabling them to guide the evolution of the main population more effectively. By dynamizing the CHTs, the proposed algorithm can adapt to a broader and more complex range of CMOPs. Additionally, state-specific optimal individual selection methods are introduced, allowing the auxiliary population to escape local optima and accelerate exploration. A simple yet effective resource allocation model is incorporated to address the potential computational resource waste associated with dual populations, enhancing the resource utilization. Comprehensive tests, including comparisons with seven state-of-the-art algorithms, were conducted on 47 benchmark functions and 12 real-world problems. The experimental results demonstrate that the proposed CMOEA outperforms existing CMOEAs in its convergence and diversity.
Mathematical Models of Critical Soft Error in Synchronous and Self-Timed Pipeline
Authors: Sokolov Igor , Stepchenkov Yuri , Diachenko Yuri , Khilko Dmitry
Published: February 2025

This paper analyzes the impact of a single soft error on the performance of a synchronous and self-timed pipeline. A nuclear particle running through the integrated circuit body is considered the most probable soft error source. The existing estimates show that self-timed circuits offer an advantage in terms of single soft error tolerance. The paper proves these estimates on the basis of a comparative probability analysis of a critical fault in two types of pipelines. The mathematical models derived in the paper describe the probability of a critical fault depending on the circuit’s characteristics, its operating discipline, and the soft error parameters. The self-timed pipeline operates in accordance with a two-phase discipline, based on the request–acknowledge interaction within the pipeline’s stages, which provides it with increased immunity to soft errors. Quantitative calculations performed on the basis of the derived mathematical models show that the self-timed pipeline has about 6.1 times better tolerance to a single soft error in comparison to its synchronous counterpart. The obtained results are in good agreement with empirical estimates of the soft error tolerance level of synchronous and self-timed circuits.
Bacteriophage Resistance, Adhesin’s and Toxin’s Genes Profile of Staphylococcus aureus Causing Infections in Children and Adolescents
Authors: Giormezis Nikolaos , Rechenioti Assimina , Doumanas Konstantinos , Sotiropoulos Christos , Paliogianni Fotini , Kolonitsiou Fevronia
Published: February 2025

Staphylococcus aureus is a common pathogen, often recovered from children’s infections. Βiofilm formation, antimicrobial resistance and production of adhesins and toxins contribute to its virulence. As resistance to antimicrobials rises worldwide, alternative therapies like bacteriophages (among them the well-studied Bacteriophage K) can be helpful. The aim of this study was to determine the bacteriophage and antimicrobial susceptibility and the presence of virulence genes among S. aureus from infections in children and adolescents. Eighty S. aureus isolates were tested for biofilm formation and antimicrobial susceptibility. The presence of two genes of the ica operon (icaA, icaD), adhesin’s (fnbA, fnbB, sasG) and toxin’s genes (PVL, tst, eta, etb) was tested by PCRs. Susceptibility to Bacteriophage K was determined using a spot assay. Thirteen isolates were methicillin-resistant (MRSA) and 41 were multi-resistant. Twenty-five S. aureus (31.3%) were resistant to Bacteriophage K, mostly from ocular and ear infections. Twelve S. aureus (15%) were PVL-positive, seven (8.8%) positive for tst, 18 (22.5%) were eta-positive and 46 were (57.5%) etb-positive. A total of 66 (82.5%) isolates carried fnbA, 16 (20%) fnbB and 26 (32.5%) sasG. PVL, tst and sasG carriage were more frequent in MRSA. Bacteriophage-susceptible isolates carried more frequently eta (32.7%) and etb (69.1%) compared to phage-resistant S. aureus (0% and 32%, respectively). Although mainly methicillin-sensitive, S. aureus from pediatric infections exhibited high antimicrobial resistance and carriage of virulence genes (especially for exfoliative toxins and fnbA). MRSA was associated with PVL, tst and sasG carriage, whereas Bacteriophage susceptibility was associated with eta and etb. The high level of Bacteriophage K susceptibility highlights its potential use against staphylococcal infections.
Molecular Recognition of Diaryl Ureas in Their Targeted Proteins—A Data Mining and Quantum Chemical Study
Authors: Aljohani Majed S. , Hu Xiche
Published: February 2025

Diaryl ureas (DU) are a cornerstone scaffold in organic and medicinal chemistry, celebrated for their unique structural attributes and broad range of biomedical applications. Their therapeutic reach has broadened beyond kinase inhibition in cancer therapy to encompass diverse mechanisms, including modulation of chromatin remodeling complexes, interference with developmental signaling pathways, and inhibition of stress-activated protein kinases in inflammatory disorders. A critical element in the rational design and optimization of DU-based therapeutics is a detailed understanding of their molecular recognition by target proteins. In this study, we employed a multi-tiered computational approach to investigate the molecular determinants of DU–protein interactions. A large-scale data mining of the Protein Data Bank resulted in an in-house dataset of 158 non-redundant, high-resolution crystal structures of DU–protein complexes. This dataset serves as the basis for a systematic analysis of nonbonded interactions, including hydrogen bonding, salt bridges, π–π stacking, CH-π, cation–π, and XH-π interactions (X = OH, NH, SH). Advanced electronic structure calculations at the B2PLYP/def2-QZVP level are applied to quantify the energetic contributions of these interactions and their roles in molecular recognition of diaryl ureas in their target proteins. The study led to the following findings: central to the molecular recognition of diaryl ureas in proteins are nonbonded π interactions—predominantly CH-π and π–π stacking—that synergize with hydrogen bonding to achieve high binding affinity and specificity. Aromatic R groups in diaryl ureas play a pivotal role by broadening the interaction footprint within hydrophobic protein pockets, enabling energetically favorable and diverse binding modes. Comparative analyses highlight that diaryl ureas with aromatic R groups possess a more extensive and robust interaction profile than those with non-aromatic counterparts, emphasizing the critical importance of nonbonded π interactions in molecular recognition. These findings enhance our understanding of molecular recognition of diaryl ureas in proteins and provide valuable insights for the rational design of diaryl ureas as potent and selective inhibitors of protein kinases and other therapeutically significant proteins.
Comparison of Exendin-4 and Its Single Amino Acid Substitutions as Parent Peptides for GLP-1 Receptor Imaging Probes
Authors: Kondo Naoya , Yonezawa Maiko , Hirano Fuko , Temma Takashi
Published: February 2025

Glucagon-like peptide-1 receptor (GLP-1R) is an emerging critical target for the diagnosis and treatment of various diseases. Radiolabeled exendin-4 (Ex-4), a GLP-1R agonist, has been widely used as an imaging probe. However, its potential to induce hypoglycemia, especially in patients with insulinoma, limits its applicability. This study evaluated whether Ex-D3, a Glu3Asp substitution of Ex-4 with a higher internalization rate, could enhance the imaging efficacy of Ex-4 while reducing its hypoglycemic effects. We synthesized derivatives with an additional C-terminal Cys (Ex-D3-C40) for site-specific 125I labeling. Surface plasmon resonance analysis revealed that C-terminus modification did not significantly alter the binding affinity of Ex-D3-C40 to GLP-1R. In vivo studies in mice demonstrated that Ex-D3-C40 induced weaker hypoglycemic effects than Ex-4-C40. Biodistribution studies showed that 125I-labeled Ex-D3 ([125I]I-Ex-D3) achieved significantly higher pancreatic accumulation and higher pancreas-to-blood and pancreas-to-muscle ratios than [125I]I-Ex-4. Ex vivo autoradiography confirmed the binding specificity of [125I]I-Ex-D3 to GLP-1R-expressing pancreatic β-cells. These findings indicate that Ex-D3 is a promising parent peptide for the development of superior GLP-1R imaging probes with reduced hypoglycemic risk, highlighting the importance of considering pharmacological effects in designing molecular imaging probes.
Evidence-Based Approach to Cerebral Vasospasm and Delayed Cerebral Ischemia: Milrinone as a Therapeutic Option—A Narrative Literature Review and Algorithm Treatment Proposition
Authors: Batarda Sena Pedro , Gonçalves Marta , Maia Bruno , Fernandes Margarida , Bento Luís
Published: February 2025

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe neurocritical condition often complicated by cerebral vasospasm (CVS), leading to delayed cerebral ischemia (DCI) and significant morbidity and mortality. Despite advancements in management, therapeutic options with robust evidence remain limited. Milrinone, a phosphodiesterase type 3 (PDE3) inhibitor, has emerged as a potential therapeutic option. Intravenous milrinone demonstrated clinical and angiographic improvement in 67% of patients, reducing the need for mechanical angioplasty and the risk of functional disability at 6 months (mRS ≤ 2). Side effects, including hypotension, tachycardia, and electrolyte disturbances, were observed in 33% of patients, occasionally leading to early drug discontinuation. Based on the evidence, we propose a treatment algorithm for using milrinone to optimize outcomes and standardize its application in neurocritical care settings.
Camellia Tea Saponin Ameliorates 5–Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation
Authors: Likitsatian Tanrada , Koonyosying Pimpisid , Paradee Narisara , Roytrakul Sittiruk , Ge Haobo , Pourzand Charareh , Srichairatanakool Somdet
Published: February 2025

Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes. Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed. Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently. Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis.
Therapeutic Potential of Gynostemma pentaphyllum Extract for Hair Health Enhancement: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Lee Jihyun , Jin Yongxun , Zhang Xinrui , Kim Myoungrae , Koh Ayoung , Zhou Shuyi , Lee Changhyun , Seo Minji , Kim Shinjae , Jo Suye , Kim Youngjoo , Kwon Seri , Kim Kyuhan , Heo Chanyeong
Published: February 2025

Background: Hair health critically influences both aesthetic appearance and psychological well-being. Existing treatments often show limited efficacy and may cause side effects. Gynostemma pentaphyllum (GP), known for its antioxidant and anti-inflammatory properties, has emerged as a promising botanical agent, although clinical evidence regarding its hair health benefits remains limited. Purpose: This study aimed to evaluate the efficacy and safety of GP extract in improving hair parameters through a randomized controlled trial. Methods: This randomized, double-blind, placebo-controlled trial involved 100 eligible adults aged 19–60 years who were randomly allocated to either the GP or placebo group. Participants consumed 340 mL/day of the test product for 24 weeks. The primary outcomes included hair elasticity, density, diameter, glossiness, and subjective satisfaction. Safety was evaluated through laboratory tests and adverse event monitoring. Results: After 24 weeks, the GP group showed a threefold increase in hair elasticity and density and a fourfold increase in hair diameter compared to the placebo group. The subjective satisfaction scores corroborated these findings: the GP users reported better outcomes in terms of reducing hair damage and dryness. No significant differences in hair glossiness were observed based on the instrumental and visual assessments (p > 0.05). The safety evaluations revealed no severe adverse events. All the safety evaluation metrics demonstrated no significant abnormalities. Conclusions: This study provides compelling evidence of the efficacy of GP extract in enhancing hair health, demonstrating both significant functional improvements and an excellent safety profile. These findings substantiate its potential as a promising functional food ingredient for comprehensive hair care interventions.
Trend in the Prevalence of Overweight, Obesity, and Body Fat Distribution in Children and Adolescents in Northwestern Argentina Between 1982 and 2019
Authors: Lomaglio Delia B. , Agüero Rosario E. Pacheco
Published: February 2025

The aim of this work was to analyze the trend of overweight, obesity, and body fat distribution of children and adolescents in Catamarca, northwest Argentina, in the last four decades. A data series obtained between 1982 and 2019 in the province of Catamarca was analyzed. The sample of 5596 individuals (46.41% female), between 5 and 14 years old, was grouped into four decades: 1980, 1990, 2000, and 2010. The categories of overweight and obesity, based on body mass index (BMI), were defined from the international reference IOTF. The fat distribution was defined according to the subscapular tricipital index (STI). Between 1980 and 2010, BMI increased by 2.35 kg/m2, overweight varied between 13.9% and 21.0%, and obesity varied between 3.4% and 19.2%. The centralized fat distribution varied from 3.9% in 1990 to 27.3% in 2010. In the cohort analysis, and after forty years, an increase in excess weight and body fat centralization was observed in children and adolescents in Catamarca. This trend was inversely proportional to the indicators of unsatisfied basic needs (UBN). It can be concluded that improvements in economic, educational, and housing conditions were not reflected in a better nutritional status.
Preclinical Retinal Disease Models: Applications in Drug Development and Translational Research
Authors: Soundara Pandi Sudha Priya , Winter Hanagh , Smith Madeleine R. , Harkin Kevin , Bojdo James
Published: February 2025

Retinal models play a pivotal role in translational drug development, bridging preclinical research and therapeutic applications for both ocular and systemic diseases. This review highlights the retina as an ideal organ for studying advanced therapies, thanks to its immune privilege, vascular and neuronal networks, accessibility, and advanced imaging capabilities. Preclinical retinal disease models offer unparalleled insights into inflammation, angiogenesis, fibrosis, and hypoxia, utilizing clinically translatable bioimaging tools like fundoscopy, optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, optokinetic tracking, and electroretinography. These models have driven innovations in anti-inflammatory, anti-angiogenic, and neuroprotective strategies, with broader implications for systemic diseases such as rheumatoid arthritis, Alzheimer’s, and fibrosis-related conditions. By emphasizing the integration of the 3Rs principles and novel imaging modalities, this review highlights how retinal research not only enhances therapeutic precision but also minimizes ethical concerns, paving the way for more predictive and human-relevant approaches in drug development.
Prodrug Approach as a Strategy to Enhance Drug Permeability
Authors: de Souza Mateus Mello , Gini Ana Luísa Rodriguez , Moura Jhonnathan Alves , Scarim Cauê Benito , Chin Chung Man , dos Santos Jean Leandro
Published: February 2025

Absorption and permeability are critical physicochemical parameters that must be balanced to achieve optimal drug uptake. These key factors are closely linked to the maximum absorbable dose required to provide appropriate plasma levels of drugs. Among the various strategies employed to enhance drug solubility and permeability, prodrug design stands out as a highly effective and versatile approach for improving physicochemical properties and enabling the optimization of biopharmaceutical and pharmacokinetic parameters while mitigating adverse effects. Prodrugs are compounds with reduced or no activity that, through bio-reversible chemical or enzymatic processes, release an active parental drug. The application of this technology has led to significant advancements in drug optimization during the design phase, and it offers broad potential for further development. Notably, approximately 13% of the drugs approved by the U.S. Food and Drug Administration (FDA) between 2012 and 2022 were prodrugs. In this review article, we will explore the application of prodrug strategies to enhance permeability, describing examples of market drugs. We also describe the use of the prodrug approach to optimize PROteolysis TArgeting Chimeras (PROTACs) permeability by using conjugation technologies. We will highlight some new technologies in prodrugs to enrich permeability properties, contributing to developing new effective and safe prodrugs.
Phase-Conjugate Feedback Effects in Electrically Pumped Semiconductor Nano-Laser Arrays
Authors: Fan Yuanlong , Zhang Jing , Shore K. Alan
Published: February 2025

An analysis is performed of the response of arrays of semiconductor nano-lasers to phase-conjugate optical feedback. A comparison is made of their response to conventional mirror feedback. It is shown that phase-conjugate feedback induces a quasi-periodic route to chaos. The impact of the Purcell-enhanced spontaneous emission, which is a salient feature of nano-lasers, is also delineated for both phase-conjugate and conventional mirror feedback.
Higher Nitrogen Uptakes Contribute to Growth Advantage of Invasive Solanum rostratum over Two Co-Occurring Natives Under Different Soil Nitrogen Forms and Concentrations
Authors: Sun Jian-Kun , Liu Ming-Chao , Chen Ji-Xin , Qu Bo , Gao Ying , Geng Lin , Zheng Li , Feng Yu-Long
Published: February 2025

High nitrogen (N) uptake is one of the main reasons for invasive alien plant invasions. However, little effort has been made to compare the effects of different N forms on N uptake between invasive and native plants, especially those on N form acquisition strategies (preference and plasticity), which influence N uptake, and thus exotic plant invasions. Related studies are particularly few in barren habitats, where the effects of N deposition on invasiveness are considered to be much weaker than in fertile habitats. In this study, we grew Solanum rostratum, a noxious invader in barren habitats, and the native plants Leymus chinensis and Agropyron cristatum in both mono- and mixed cultures under nitrate and ammonium addition treatments, and analyzed the effects of the soil N availability and forms on the growth, N uptake, and N form acquisition strategies for these plants. The invader outperformed the natives in N uptake (in most cases) and growth (always) in both mono- and mixed cultures under all N treatments. N addition increased the N uptake and growth of the invader. The advantages of the invader over the natives were higher under ammonium relative to nitrate addition. The growth advantage of the invader was associated with its higher N uptake and higher N-use efficiency. Higher plasticity in N form uptake may contribute to the higher N uptake for the invader when grown in mixed cultures. Our findings indicate that N deposition, particularly in the form of ammonium, may accelerate exotic plant invasions in barren habitats.
Three New Records of Pathogens Causing Stem Blight on Vaccinium corymbosum in China
Authors: Zhou Yueyan , Wu Linna , Ren Kaixuan , Wang Meng , Wang Nannan , Tangtrakulwanich Khanobporn , Li Xinghong , Chethana Kandawatte Wedaralalage Thilini , Hyde Kevin D. , Zhang Wei , Yan Jiye
Published: February 2025

Stem blight is a significant disease affecting blueberries worldwide, caused by various pathogens. This study investigated stem blight disease in Ji’an, Jilin Province, China. Fungi isolated from diseased stems were identified as Colletotrichum temperatum, Curvularia austriaca, and Diaporthe unshiuensis based on morphological characters and multi-locus phylogenetic analyses using the internal transcribed spacer (ITS) region, glyceraldehyde 3-phosphate dehydrogenase (gapdh), chitin synthase (chs), actin (act), β-tubulin (tub2), the translation elongation factor 1-alpha (tef1-α), calmodulin (cal), and histone 3 (his3) regions. Pathogenicity test was conducted on detached green blueberry shoots, all shoots inoculated by mycelium plugs presented necrotic lesions with dark brown margins, while the control (PDA plugs) group did not show any symptoms. Koch’s postulates were confirmed by re-isolating the inoculated pathogen from the disease symptoms. The study provides three new host–pathogen records of fungi associated with blueberry stem blight.
Comprehensive Chloroplast Genomic Insights into Amaranthus: Resolving the Phylogenetic and Taxonomic Status of A. powellii and A. bouchonii
Authors: Han Jizhe , Lin Chuhang , Zhu Tingting , Liu Yonghui , Yan Jing , Qi Zhechen , Yan Xiaoling
Published: February 2025

Amaranthus, a genus in Amaranthaceae, is divided into three subgenera—Amaranthus, Acnida, and Albersia—and contains approximately 70 to 80 species. Understanding its phylogenetic relationships is essential for species classification, genetic diversity assessment, and evolutionary studies. This knowledge is vital for improving Amaranthus utilization in crop improvement and managing the ecological impacts of invasive weeds. In this study, we analyzed the chloroplast genomes of 27 Amaranthus species across all three subgenera to characterize their genomic features and construct a comprehensive phylogenetic tree. Our aim was to elucidate the phylogenetic relationships within the genus and evaluate interspecific affinities among the subgenera. We also addressed the taxonomic ambiguity surrounding A. bouchonii and A. powellii to determine their distinct species within the genus. Chloroplast genome sizes ranged from 149,949 to 150,818 bp, with GC content varying between 36.52% and 36.63%. Comparative structural analyses confirmed highly conserved quadripartite structures, gene content, and organization, comprising 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. Repeat and codon usage analyses revealed conserved repeat patterns and a preference for codons ending in A or U. Selection pressure analysis indicated a predominantly purifying selection, with matK showing signs of positive selection, particularly in A. spinosus. Phylogenetic analysis of 80 protein-coding genes confirmed the monophyly of subgenus Amaranthus but found Alberisa and Acnida to be paraphyletic. Despite their morphological similarity, A. bouchonii and A. powellii were placed in separate clades within subgenus Amaranthus, with A. bouchonii clustering with A. retroflexus, and A. powellii aligning with the A. hybridus complex. Additionally, we identified 16 variable regions as potential molecular markers for species identification. Our study provides the most comprehensive Amaranthus chloroplast genome dataset to date, offering new insights into its evolutionary relationships and valuable genomic resources for taxonomy, germplasm management, and invasive risk assessment.
Bacteriostatic Activity and Resistance Mechanism of Artemisia annua Extract Against Ralstonia solanacearum in Pepper
Authors: Du Tiantian , Zhu Weiping , Zhang Chenning , Liang Xiaomin , Shu Yinghua , Zhou Jingyun , Zhang Mengyu , He Yuxuan , Tu Jincai , Feng Yuanjiao
Published: February 2025

The destructive bacterial wilt disease caused by Ralstonia solanacearum leads to substantial losses in pepper production worldwide. Plant-derived pesticides exhibit advantages of high efficiency and broad spectrum when compared to traditional chemical pesticides. Artemisia annua and ‘Tai Jiao’ No. 1 were used as the experimental materials, and treated with 0.75 g·mL−1, 1.5 g·mL−1, and 3 g·mL−1 of A. annua extract and inoculated with R. solanacearum at a concentration of OD600 = 0.1 for 14 days. The inhibitory activity of A. annua extracts against R. solanacearum, as well as the disease index, defense enzyme activities, and defense-related substances contents of pepper seedlings were determined. The results showed that the Minimum Inhibitory Concentration (MIC) of the A. annua extract was 3 g·mL−1. As the concentration of A. annua extract increased, the extent of R. solanacearum cell crumpling intensified, accompanied by a gradual decline in its biofilm-forming ability. On the 14th day after treatment, the disease severity index and incidence rate were significantly reduced when the A. annua extract was applied at concentrations of 0.75 g·mL−1 and 3 g·mL−1. At both the 7th and 14th days after treatment, the application of A. annua extract at concentrations of 0.75 g·mL−1 and 3 g·mL−1 led to enhanced activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in peppers at different stages. Simultaneously, it reduced the levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), effectively scavenging reactive oxygen species and alleviating cellular lipid peroxidation. Furthermore, the extract increased the activities of polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL), as well as elevated the contents of soluble protein, flavonoids, and total phenols, ultimately enhancing the disease resistance of peppers. Considering the development costs, the application of A. annua extract at a concentration of 0.75 g·mL−1 demonstrates great potential for green control measures against bacterial wilt in peppers.
Study on the Relationships Between Calcium Accumulation in Fruits and Calcium Dynamics in Fruit Stalks During the Development and Ripening of Cerasus humilis Fruit
Authors: Zhang Li , Zhang Wei , Guo Jinli
Published: February 2025

Cerasus humilis is a unique fruit tree renowned for its exceptional calcium content. To investigate the relationship between calcium absorption and accumulation in the fruit, as well as the dynamic changes in calcium within the fruit stalks during development and maturation, this study examined the content and proportion of different forms of calcium in the fruits and fruit stalks under different Cerasus humilis types and 2,4-D treatment. Additionally, the characteristics of the calcium concentration difference ratio between the fruit stalks and fruits were analyzed. Given that the study is based on a single year of data, this preliminary research explores the calcium transport relationship between the fruit stalks and fruits, providing a foundation for more extensive future research. The results revealed that the content and proportion of water-soluble calcium in fruits and fruit stalks gradually increased during development. In contrast, the content and proportion of other calcium forms, such as calcium oxalate and calcium phosphate, showed a downward trend. This decline was more pronounced in the fruits than in the fruit stalks. Treatment with 2,4-D significantly increased the content of all calcium components in the fruits, reduced the proportion of calcium oxalate and calcium phosphate in the fruit stalks, and increased their proportion in the fruits. The changes in calcium forms between the fruits and fruit stalks were closely interrelated, with 2,4-D treatment enhancing the correlation between the contents of calcium phosphate and calcium oxalate in both tissues. The calcium concentration in the fruit stalks is significantly higher than in the fruits, showing a noticeable calcium concentration difference ratio, with water-soluble calcium exhibiting the smallest difference and calcium oxalate and calcium phosphate displaying the largest. Treatment with 2,4-D significantly reduced the calcium concentration difference ratio between the fruit stalks and the fruits. In conclusion, the periods from the young fruit stage to the hard seed stage and from the hard–ripe stage to the fully ripe stage are critical for calcium transformation, transport, and accumulation. Different calcium forms in the fruits and fruit stalks can interconvert, with water-soluble calcium being more readily transported to the fruits. In contrast, calcium oxalate and calcium phosphate tend to accumulate in the fruit stalks. Calcium pectin behaves differently in the two types of Cerasus humilis. In MY-2, it is more readily transported to the fruit, while in MY-9, it tends to accumulate in the fruit stalks. Treatment with 2,4-D facilitates the transport of calcium from the fruit stalks to the fruits, enhances calcium content in the fruits, and optimizes calcium distribution.
Comparative Performance Evaluation of YOLOv5, YOLOv8, and YOLOv11 for Solar Panel Defect Detection
Authors: Khanam Rahima , Asghar Tahreem , Hussain Muhammad
Published: February 2025

The reliable operation of photovoltaic (PV) systems is essential for sustainable energy production, yet their efficiency is often compromised by defects such as bird droppings, cracks, and dust accumulation. Automated defect detection is critical for addressing these challenges in large-scale solar farms, where manual inspections are impractical. This study evaluates three YOLO object detection models—YOLOv5, YOLOv8, and YOLOv11—on a comprehensive dataset to identify solar panel defects. YOLOv5 achieved the fastest inference time (7.1 ms per image) and high precision (94.1%) for cracked panels. YOLOv8 excelled in recall for rare defects, such as bird drops (79.2%), while YOLOv11 delivered the highest mAP@0.5 (93.4%), demonstrating a balanced performance across the defect categories. Despite the strong performance for common defects like dusty panels (mAP@0.5 > 98%), bird drop detection posed challenges due to dataset imbalances. These results highlight the trade-offs between accuracy and computational efficiency, providing actionable insights for deploying automated defect detection systems to enhance PV system reliability and scalability.
Biophilic Design Strategies and Indoor Environmental Quality: A Case Study
Authors: Asojo Abimbola , Hazazi Fullah
Published: February 2025

Sustainability in the built environment seeks to balance ecological responsibility with human health and well-being. Biophilic design, a key strategy within sustainable architecture that emphasizes connections with nature, has emerged as a promising approach to enhancing Indoor Environmental Quality (IEQ) and promoting occupant well-being. However, while biophilic design has been widely studied in various settings, its application in workplace environments within public buildings, particularly museums, remains underexplored. This research addresses this gap by investigating biophilic design strategies integrated in the Bell Museum in St. Paul, Minnesota, and their impact on IEQ, occupant satisfaction, work performance, and health. Utilizing the Sustainable Post-Occupancy Evaluation Survey (SPOES) based on the B3 Minnesota Sustainable Building Guidelines, this study assesses employee perceptions of their health and well-being in the built environment. The findings reveal high satisfaction (M = 6.29) with the physical environment, a positive impact on work performance (M = 5.89), and improved overall health (M = 5.35). The authors examine how the Bell Museum’s adaptation of Terrapin’s 14 Patterns of Biophilic Design, identifying effective strategies such as natural light, material connections with nature, and spatial configuration. While these elements contribute to an enhanced indoor environment, the study also identifies areas for improvement, including the absence of certain biophilic patterns, such as biomorphic forms and multisensory elements, and complexity and order, which could further enrich occupant experience. The study underscores the role of biophilic principles in shaping indoor environments and suggests that future research explore additional strategies to enhance well-being.
Digital Finance, Digital Usage Divide, and Urban–Rural Income Gap: Evidence from China
Authors: Xiao Yanfei , Yin Mengli , Wang Huilin , Xiang Yunbo
Published: February 2025

Digital finance can reduce the urban–rural income gap, but the digital divide may limit this effect. This study develops a theoretical framework to explore the interactions between digital finance, the digital usage gap, and income disparity. Using data from 274 Chinese cities, the research applies a two-way fixed-effects and threshold effect model. The results indicate that disparities in digital usage not only diminish but may also distort the convergence benefits of digital finance, producing a U-shaped relationship that exhibits variability across dimensions and regions. Additionally, traditional financial systems appear to moderate this U-shaped pattern by delaying the point at which digital finance begins to widen the urban–rural income gap. However, the extent of this alleviation is influenced by the digital usage is divisive. Once digital technology adoption exceeds a threshold, the negative effect becomes positive, narrowing the urban–rural income gap. Consequently, policy initiatives should prioritize improving financial conditions in rural areas, accelerating the digital transformation of conventional finance, bolstering digital education in rural regions, and addressing the disparities in digital usage.
Influence of Tetrabromobisphenol-A on the Fate and Behavior of Zinc Oxide Nanoparticles Affected by Salts, Humic Acid, and Bovine Serum Albumin in Water Systems
Authors: Khan Anwar Ul Haq , Liu Yanju , Naidu Ravi , Fang Cheng , Shon Ho Kyong
Published: February 2025

The environmental release of zinc oxide nanoparticles (ZnO-NPs) may have consequences for ecosystems. The behavior and environmental effects of ZnO-NPs could change due to their interactions with other existing substances. This research explored how the presence of coexisting organic pollutants (like tetrabromobisphenol-A (TBBPA)), electrolytes (such as NaCl and CaCl2), natural organic materials (including humic acid (HA)), and bovine serum albumin (BSA) in simulated water affected the behavior of ZnO-NPs. Various characterization techniques were used to analyze the size, shape, purity, crystallinity, and surface charge of ZnO-NPs following interactions (after one day, one week, two weeks, and three weeks) at pH 7. The findings demonstrated changes in both the size and zeta potential of the ZnO-NPs in isolation and when TBBPA and electrolytes were included in the suspension. The size and surface charge exhibited different variations across fixed concentrations (5 mM) of various electrolytes. HA and BSA contributed to the dispersion of ZnO-NPs by affecting the zeta potential. These dispersion effects were also observed in the presence of TBBPA and salts, attributed to their substantial aliphatic carbon content and complex structures. Potential interaction forces that could explain the adsorption of TBBPA include cation bridging, hydrophobic interactions, hydrogen bonding, electrostatic interactions, and van der Waals forces. The co-occurrence of organic pollutants (TBBPA) and natural organic compounds (HA and BSA) can alter the surface properties and behavior of ZnO-NPs in natural and seawater, aiding in the understanding of the fate and impact of engineered nanoparticles (such as ZnO-NPs) in the environment.