bluuebunny/crossref_metadata_2025 huggingface dataset:
Depolymerization of PET with n-Hexylamine, n-Octylamine, and 3-Amino-1-Propanol, Affording Terephthalamides
Authors: Hiruba Sumiho , Ogiwara Yohei , Nomura Kotohiro
Published: January 2025

The chemical conversion of plastic waste has been considered an important subject in terms of the circular economy, and the chemical recycling and upcycling of poly(ethylene terephthalate) (PET) has been considered one of the most important subjects. In this study, the depolymerization of PET with n-hexylamine, n-octylamine, and 3-amino-1-propanol has been explored in the presence of Cp*TiCl3 (Cp* = C5Me5). The reactions of PET with n-hexylamine and n-octylamine at 130 °C afforded the corresponding N,N′-di(n-alkyl) terephthalamides in high yields (>90%), and Cp*TiCl3 plays a role as the catalyst to facilitate the conversion in exclusive selectivity. The reaction of PET with 3-amino-1-propanol proceeded at 100 °C even in the absence of the Ti catalyst, affording N,N′-bis(3-hydroxy) terephthalamides in high yields. A unique contrast has been demonstrated between the depolymerization of PET by transesterification with alcohol and by aminolysis; the depolymerizations with these amines proceeded without the aid of a catalyst.
Unveiling the Molecular Mechanisms Underlying the Success of Simple Limbal Epithelial Transplantation (SLET)
Authors: Garg Aastha , Goel Kartik , Gour Abha , Sapra Mehak , Sangwan Virender Singh , Tripathi Ratnakar , Tiwari Anil
Published: January 2025

Simple limbal epithelial transplantation (SLET) has emerged as an effective treatment option for limbal stem cell deficiency (LSCD). However, the precise molecular mechanisms underlying its success remain incompletely understood. This review delves into the proposed mechanisms involving the donor limbus, host microenvironment, and the amniotic membrane as a scaffold in SLET. The donor limbus contributes to SLET efficacy through various factors secreted by limbal epithelial stem cells, including hepatocyte growth factor (HGF), soluble Fms-like tyrosine kinase-1 (sFLT-1), and pigment epithelium-derived factor (PEDF), which support corneal healing and transparency. Additionally, the presence of melanocytes, immune cells, limbal fibroblasts, and adhesion molecules within the donor tissue helps preserve the integrity of the limbal niche. The host environment plays a critical role in supporting the transplanted stem cells, with mesenchymal stem cell-secreted factors promoting proliferation and differentiation. Although the amniotic membrane has traditionally been used as a scaffold, emerging evidence suggests that it may not always be necessary. Further studies are needed to validate this scaffold-free approach and to evaluate the vitality and functional contributions of individual components used in SLET. Understanding these complex interactions and molecular mechanisms sheds light on the importance of the donor tissue, host microenvironment, and scaffold in SLET, paving the way for the optimization of this technique for the effective treatment of LSCD.
Odontogenic Myxoma Associated to Unerupted Mandibular Molar in a Pediatric Patient: A New Case Description with Comprehensive Literature Analysis
Authors: Forte Marta , D’Albis Giuseppe , d’Amati Antonio , Ingravallo Giuseppe , Limongelli Luisa , Favia Gianfranco , Di Grigoli Adriano , Montaruli Anna , Di Venere Daniela , Corsalini Massimo , Capodiferro Saverio
Published: January 2025

Background/Objectives: Odontogenic tumors in pediatric patients are uncommon; among all, the intraosseous occurrence of odontogenic myxoma is very rare, accounting for almost 8.5–11.6% of all odontogenic tumors in children. The radiological appearance is highly variable and is often responsible for the diagnostic delay and treatment. Methods: We report a case of odontogenic myxoma occurring in the posterior mandible of a 12-year-old female, found on a panoramic radiograph performed for the delayed eruption of the second inferior molar, treated by conservative surgery. A comprehensive analysis of the literature was also carried out. Results: The radiological features of the presented case were unique, as the lesion was encompassed within the uncompleted (developing) dental crown still unerupted, as confirmed by the macroscopic appearance. Then, the differential diagnosis included odontogenic fibroma, immature dental pulp or follicle from a developing tooth, and ameloblastic fibrodontoma. The histological examination led to the final diagnosis of odontogenic myxoma. As for the literature analysis, after a PRISMA-based selection of the papers, a total of 23 articles (case reports and case series on odontogenic myxomas in pediatric patients, a total of 33 cases) were finally selected and studied; all the pertinent data are widely discussed within the paper. Conclusions: The current case highlights the importance of the radiological investigation in pediatric patients when a delayed eruption lasts for several months, leading to an early diagnosis necessary to avoid more aggressive surgical therapies and possible recurrence; data from the literature about site of occurrence, sex, age, kind of surgical procedure, and recurrence rate are discussed too.
Body Weight Perception and Other Factors Associated with Overweight and Obesity in U.S. Adolescents
Authors: Shah Gulzar , Karibayeva Indira , Shankar Padmini , Mason Semon , Griffin J. Michael
Published: January 2025

Background/Objectives: This study examines the factors associated with U.S. adolescents’ obesity and overweight status. Methods: Using a multivariable logistic regression, we analyzed the data from the 2021 Youth Risk Behavior Surveillance System (YRBSS), comprising 17,232 students. Results: The odds of being obese or overweight were significantly higher (p ≤ 0.05) for the participants who perceived themselves as slightly overweight (AOR, 13.31; 95% CI [11.83, 14.97]) or very overweight (AOR, 39.29; 95% CI [30.12, 51.25]) compared to those who perceived their weight as about right. The participants with significantly higher odds included those aged 14 years (AOR, 2.53) compared to those aged 13 years or younger; male students (AOR, 1.63) compared to female students; and American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander students (AOR, 2.11), Black or African American students (AOR, 2.63), Hispanic/Latino students (AOR, 1.54), and students of multiple races (AOR, 1.56), compared to White students. The odds were also significantly higher for the participants who did not eat breakfast on all seven days of a week (AOR, 1.21) and for the students who did not report their mental health status (AOR, 2.07) compared to those who reported their mental health as mostly or always not good. Conclusions: These findings suggest schools are uniquely positioned to implement strategies for healthier behaviors designed and implemented with a focus on health equity.
Corrosion Behavior and Mechanism of High-Aluminum Inconel 625 in Chlorinated Salts
Authors: Wei Ying , Cao Junjia , Zheng Yuehong , Yu Haicun , Yang Penghui , La Peiqing
Published: January 2025

Concentrated solar power plant (CSP) technology holds significant application value in the renewable energy sector for converting solar radiation into thermal and electrical energy. As a heat storage medium for next-generation solar thermal power stations, chloride salts exhibit strong corrosive effects on structural components. To enhance corrosion resistance of the heated body in molten salt environments, Inconel 625 is modified by incorporating aluminum, which facilitates the formation of a protective oxide film. In this study, High-Aluminum Inconel 625, after cold rolling and solution treatment, was immersed in a NaCl-KCl-MgCl2 eutectic chloride melt at 650 °C for 200 h. Post-corrosion analysis revealed the formation of an alumina layer on the surface, effectively mitigating corrosion. Increased aluminum content resulted in thicker alumina layers and the formation of oxidation products, such as Cr2O3, Fe2O3, MoO2, and MgCr2O4 spinel structures, significantly enhancing the alloy’s corrosion resistance. The Inconel 625 cold-rolled plate with 5.31 wt% Al exhibited the best corrosion resistance (3510 μm/year), making it a promising candidate for use in next-generation CSP heat storage and exchange components.
Mathematical Modeling to Predict the Formation of Micrometer-Scale Crystals Using Reverse Anti-Solvent Crystallization
Authors: Wang Jianhua , Wang Fawei , Wen Xu , Zhang Yankang , Wang Jiapeng , Liu Yucun
Published: January 2025

The reverse addition process in anti-solvent crystallization is safer and more efficient than sieving when dealing with energetic compounds. A new mathematical model has been developed to understand the crystal size mechanism during the reverse addition of solvent in a binary system. This model incorporates droplet dynamics, distribution moments, and mass balance constraints. It can be used to predict the appropriate crystal size for designing explosive recipes with a desired particle size distribution to maximize energy output. The model was validated by conducting reverse-addition crystallization of sodium chloride in a deionized water/ethanol binary system at temperatures ranging from 10 to 50 degrees Celsius. The predicted results closely matched the experimental findings, which were confirmed using a Laser Particle Size Analyzer and Electron Microscope Scanning.
Bacterial Diversity and Composition in the Internal Organs of Taiga Bean Goose, Greater White-Fronted Goose and Willow Ptarmigan as a New Tools in the Arctic Biomonitoring System
Authors: Durnova Evdokia , Karmanova Elena , Sorokina Tatiana , Mayorova Ksenia , Aksenov Andrey
Published: January 2025

Birds, fish, and marine mammals consumed by indigenous people are included in Arctic biomonitoring. However, there are still many gaps in the data on the microbiota associated with these animals. In the current study, we used high-throughput 16S rRNA gene sequencing to explore the bacterial diversity and composition in the intestines of willow ptarmigans, greater white-fronted geese, and taiga bean geese, which are widely consumed by indigenous people in the Arctic. For the first time, meta-taxonomic data have been obtained on the lungs of wild resident and migratory birds of the Russian North. The potentially pathogenic bacterial genera Helicobacter and Olsenella were found in the intestinal microbiomes of three bird species and in the lungs of willow ptarmigan. Bacteria of the genus Staphylococcus were individually identified in the intestines of willow ptarmigan, Campylobacter sp. in the intestines of taiga bean goose, and Sutterella sp. in the intestines of greater white-fronted goose as potential pathogens. The primary findings will be used to propose a next-generation sequencing scheme for monitoring both chemical and biological contaminants in the Arctic in line with One Health approach.
A Broadband Mode Converter Antenna for Terahertz Communications
Authors: Paudel Biswash , Li Xue Jun , Seet Boon-Chong
Published: January 2025

The rise of artificial intelligence (AI) necessitates ultra-fast computing, with on-chip terahertz (THz) communication emerging as a key enabler. It offers high bandwidth, low power consumption, dense interconnects, support for multi-core architectures, and 3D circuit integration. However, transitioning between different waveguides remains a major challenge in THz systems. In this paper, we propose a THz band mode converter that converts from a rectangular waveguide (RWG) (WR-0.43) in TE10 mode to a substrate-integrated waveguide (SIW) in TE20 mode. The converter comprises a tapered waveguide, a widened waveguide, a zigzag antenna, and an aperture coupling slot. The zigzag antenna effectively captures the electromagnetic (EM) energy from the RWG, which is then coupled to the aperture slot. This coupling generates a quasi-slotline mode for the electric field (E-field) along the longitudinal side of the aperture, exhibiting odd symmetry akin to the SIW’s TE20 mode. Consequently, the TE20 mode is excited in the symmetrical plane of the SIW and propagates transversely. Our work details the mode transition principle through simulations of the EM field distribution and model optimization. A back-to-back RWG TE10-to-TE10 mode converter is designed, demonstrating an insertion loss of approximately 5 dB over the wide frequency range band of 2.15–2.36 THz, showing a return loss of 10 dB. An on-chip antenna is proposed which is fed by a single higher-order mode of the SIW, achieving a maximum gain of 4.49 dB. Furthermore, a balun based on the proposed converter is designed, confirming the presence of the TE20 mode in the SIW. The proposed mode converter demonstrates its feasibility for integration into a THz-band high-speed circuit due to its efficient mode conversion and compact planar design.
Analysis of Kazakhstan Oil Shale Deposits in Accordance with Resource Estimation Practices for Consideration of Potential Shale Oil Reserves
Authors: Sabanov Sergei , Konist Alar , Korshunova Ruslana
Published: January 2025

Most oil shale deposits in Kazakhstan were estimated without detailed calculations of the grade and tonnages and included low confidence categories, i.e., Inferred, Off-Balance, and Non-Economic oil shales, on which cannot be given any oil reserves. An analysis of Kazakhstan oil shale deposits in accordance with resource estimation practices for consideration of potential shale oil tonnages has been produced. The developed methodology considers extraction and processing recoveries of conventional and unconventional mining methods. The methodology uses Monte Carlo modeling to estimate a range of oil content and oil recoveries and uses the event tree analysis to demonstrate how the initial oil shale material tonnages and grades go through various fault and success branches, considering probabilities distributions and estimating potential shale oil tones at the end. As a result, this estimation methodology has been validated by high-ranked resource category oil shale deposits, which demonstrated the range of potential shale oil in the range of 10.7–16.8 Mt at the 50% confidence level. The results will be used for further consideration in financial-economic feasibility studies, which must take into account operational and capital expenses, product sale prices and market, and social-environmental aspects.
Optimization of Well Locations and Trajectories: Comparing Sub-Vertical, Sub-Horizontal and Multi-Lateral Well Concepts for Marginal Geothermal Reservoir in The Netherlands
Authors: Barros Eduardo G. D. , Szklarz Slawomir P. , Khoshnevis Gargar Negar , Wollenweber Jens , van Wees Jan Diederik
Published: January 2025

Scaling up the direct use of geothermal heat in urban areas comes with the challenge of enabling the development of projects in geological settings where geothermal reservoir flow properties may be poor, resulting in low well flow performance. Cost-effective field development strategies and well designs tailored to such reservoirs can ensure the deliverability of geothermal energy in economic terms. This study presents a framework based on computer-assisted optimization to support practitioners in selecting the most suitable well concept for the exploitation of such marginal geothermal reservoirs. The proposed methodology is illustrated in a real-life case study of a geothermal development prospect in an urban area in The Netherlands, where the performance of sub-vertical, sub-horizontal and multi-lateral wells is compared. The obtained results indicate that the techno-economic performance of the geothermal doublet can be significantly improved by optimization, for all considered well concepts, and that, despite the importance of selecting the well concept, well location is still the main determinant of an effective field development strategy. The sub-horizontal and multi-lateral well concepts appear to be the most suitable for the target case study, outperforming the sub-vertical doublets, with a higher expected net present value and a lower economic variability risk for the multi-lateral solution.
Where Do Fires Burn More Intensely? Modeling and Mapping Maximum MODIS Fire Radiative Power from Aboveground Biomass by Fuel Type in Mexico
Authors: Tinoco-Orozco Diana Aime , Vega-Nieva Daniel José , Briseño-Reyes Jaime , Dominguez-Amaya Mesías Edwin , Silva-Cardoza Adrián Israel , Briones-Herrera Carlos Ivan , Álvarez-González Juan Gabriel , Corral Rivas José Javier , López-Serrano Pablito Marcelo , Jardel-Pelaez Enrique J. , Perez-Salicrup Diego , Ruiz-González Ana Daría
Published: January 2025

Mapping potential fire intensity is a fundamental tool for fire management planning. Despite the wide use of Fire Radiative Power (FRP) as an indicator of expected fire intensity and fire emissions, very few studies have spatially analyzed the role of remotely sensed proxies of vegetation productivity to explain FRP. The current study aimed at modeling and mapping the relationships between aboveground biomass and Moderate Resolution Imaging Spectroradiometer (MODIS) maximum FRP, at 1 km pixel, in 2011–2020, for each of 46 fuel regions in the entirety of Mexico. Maximum FRP–biomass relationships supported a novel hypothesis of varying constraints of fire intensity. In lower-productivity areas, such as semiarid shrub- and grass-dominated ecosystems, fine fuel loads limited fire occurrence and FRP was positively related to biomass. In the more productive areas, such as temperate or tropical forests, a humped relationship of FRP against biomass was observed, suggesting an intermediate-productivity hypothesis of maximum fire intensity within those regions. In those areas, the highest fire intensity was observed in the intermediate biomass areas, where surface (timber understory) and crown fuel availability, together with higher wind penetration, can result in crown fires. On the contrary, within the most productive areas, the lowest intensity occurred, likely due to weather and fuel (timber litter) limitations.
Novel Fermented Plant-Based Functional Beverage: Biological Potential and Impact on the Human Gut Microbiota
Authors: Vila-Real Catarina , Costa Célia , Pimenta-Martins Ana , Mbugua Samuel , Hagrétou Sawadogo-Lingani , Katina Kati , Maina Ndegwa H. , Pinto Elisabete , Gomes Ana M. P.
Published: January 2025

Controlled fermentation carried out by selected starters might enhance the safety, nutritional, and biological profiles of non-dairy fermented products. This research aims to study the biological potential and impact on the human gut microbiota of a novel fermented finger millet-based product. Finger millet (Eleusine coracana), suspended in an aqueous sucrose-based solution, was fermented by Weissella confusa 2LABPT05 and Lactiplantibacillus plantarum 299v (1%, 1:1 ratio (v/v)), at 30 °C/200 rpm in an orbital incubator until pH ≈ 4.5–5.0. Microbial growth, phenolic compounds, antioxidant, and antidiabetic activities were evaluated. In vitro digestion followed by in vitro faecal fermentation were used to study the impact of the fermented plant-based functional beverage (PBFB) on the human gut microbiota. Antidiabetic activity (21% vs. 14%) and total phenolics (244 vs. 181 mg of gallic acid equivalents/kg PBFB) increased with fermentation. The digested fermented PBFB contributed to the increase, over the first 6 h, of the Bifidobacterium’s 16S rRNA gene copy numbers, concomitant with significant release of the acetic, propionic, and butyric short chain fatty acids, and also lactic acid. The novel PBFB has been shown to have antidiabetic potential and bifidogenic effects, and consequently its consumption might positively impact blood glucose levels and the human gut microbiota.
Clarification of Sugarcane Juice Catalyzed by Magnetic Immobilized Laccase Intensified by Alternating Magnetic Field
Authors: Wang Feng , Wang Mingtong , Wang Miaomiao , Xu Ling , Qian Jingya , Guan Guoqiang , Xu Baoguo
Published: January 2025

In this study, Cu2+-chelated magnetic silicon dioxide nanoparticles were synthesized as carriers for laccase immobilization. The prepared magnetic immobilized laccase was applied in the clarification of sugarcane juice. The optimal conditions for the clarification of sugarcane juice with magnetic immobilized laccase in a shake flask were determined to be as follows: a temperature of 35 °C, pH of 5.5, rotation speed of 150 r/min, and immobilized laccase dosage of 1.0 mg/mL. The sucrose in the sugarcane juice inhibited both free and immobilized laccase. The inhibitory effect was characterized as mixed inhibition, wherein competitive inhibition played a dominant role. An alternating magnetic field was introduced into the catalysis process using magnetic immobilized laccase, and the catechin degradation rate was improved to 77.2% under a magnetic field intensity of 80 Gs and magnetic field frequency of 400 Hz. Under the optimal alternating magnetic field conditions, the treatment time of sugarcane juice was reduced to 20 min when catalyzed by the magnetic immobilized laccase, wherein a decolorization rate of 54.4%, reduction in turbidity of 89.7%, and total phenol degradation rate of 43.4% were achieved. Compared with the shaking condition, the assistance of alternating magnetic fields can shorten the clarifying time, increase the clarifying effect, and enhance the catalyst reusability. These results reveal useful information about the enzymatic treatment of high-sugar juice and provide a potential strategy for juice clarification with magnetic immobilized enzymes.
Type 1 Diabetes Risk Variants Reduce Beta Cell Function
Authors: Ratajczak Wiktoria , Jones Angus G. , Atkinson Sarah D. , Kelly Catriona
Published: January 2025

Introduction: The variants rs10517086 and rs1534422 are predictive of type 1 diabetes mellitus (T1DM) development and poor residual β cell function within the first year of diagnosis. However, the mechanism by which risk is conferred is unknown. We explored the impact of both variants on β cell function in vitro and assessed their relationship with C-peptide in people with T1DM and type 2 diabetes mellitus (T2DM). Methods: Using CRISPR/Cas9, the variants were introduced into a β cell line (BRIN-BD11) and a T cell line (Jurkat cells) from which the conditioned media was applied to otherwise healthy β cells to model the inflammatory environment associated with these variants. Results: Both variants significantly reduced glucose-stimulated insulin secretion, increased production of pro-inflammatory cytokines and reduced expression of several β cell markers and transcription factors (KCNJ11, KCNQ1, SCL2A2, GCK, NKX6.1, Pdx1 NGN3). However, HNF1A was significantly upregulated in the presence of both variants. We subsequently silenced HNF1A in variant expressing BRIN-BD11 cells using siRNA and found that gene expression profiles were normalised. Induction of each variant significantly increased expression of the lncRNAs they encode, which was normalised upon HNF1A silencing. Analysis of the DARE (Diabetes Alliance for Research in England) study revealed an association of rs10517086_A genotype with C-peptide in 153 individuals with T1DM, but not in 417 people with T2DM. Conclusions: These data suggest that rs1534422 and rs10517086 exert multiple insults on the β cell through excessive upregulation of HNF1A and induction of pro-inflammatory cytokines, and highlight their utility as prognostic markers of β cell function.
Upgrading a Low-Cost Seismograph for Monitoring Local Seismicity
Authors: Vlachos Ioannis , Anagnostou Marios N. , Avlonitis Markos , Karakostas Vasileios
Published: January 2025

The use of a dense network of commercial high-cost seismographs for earthquake monitoring is often financially unfeasible. A viable alternative to address this limitation is the development of a network of low-cost seismographs capable of monitoring local seismic events with a precision comparable to that of high-cost instruments within a specified distance from the epicenter. The primary aim of this study is to compare the performance of an advanced, contemporary low-cost seismograph with that of a commercial, high-cost seismograph. The proposed system is enhanced through the integration of a 24-bit analog-to-digital converter board and an optimized architecture for a low-noise signal amplifier employing active components for seismic signal detection. To calibrate and assess the performance of the low-cost seismograph, an installation was deployed in a region of high seismic activity in Evgiros, Lefkada Island, Greece. The low-cost system was co-located with a high-resolution 24-bit commercial digitizer, equipped with a broadband (30 s—50 Hz) seismometer. An uninterrupted dataset was collected from the low-cost system over a period of more than two years, encompassing 60 local events with magnitudes ranging from 0.9 to 3.2, epicentral distances from 5.71 km to 23.45 km, and focal depths from 1.83 km to 19.69 km. Preliminary findings demonstrate a significant improvement in the accuracy of earthquake magnitude estimation compared to the initial configuration of the low-cost seismograph. Specifically, the proposed system achieved a mean error of ±0.087 when benchmarked against the data collected by the high-cost commercial seismograph. These results underscore the potential of low-cost seismographs to serve as an effective and financially accessible solution for local seismic monitoring.
In Vitro Propagation of Peumus boldus Molina Using a Temporary Immersion System
Authors: Guerra Francesca , Badilla Loreto , Cautín Ricardo , Castro Mónica
Published: January 2025

Peumus boldus Mol. (boldo) is a Chilean endemic tree species, characteristic of the region’s sclerophyllous forests. Increasing demand for its leaves and bark, valued for their antioxidant properties, has contributed to declining populations of this species in its natural habitat. This decline is further exacerbated by low natural germination rates and anthropogenic pressures. To support conservation efforts, efficient mass propagation protocols are needed. This study pioneered the use of temporary immersion systems (TIS) for the in vitro propagation of boldo, successfully developing a novel mass propagation protocol. To optimize the in vitro propagation of boldo shoots using the temporary immersion system (TIS), various immersion durations were tested. While a 3 min immersion resulted in a high proliferation rate (10.8), it also induced shoot vitrification, a detrimental physiological disorder. However, reducing the immersion duration to 2 min successfully prevented vitrification while still achieving a satisfactory multiplication rate of 7.2. The shoots reached an average length of 6.1 to 6.4 cm with 6-benzylaminopurine (4.44 μM). Ex vitro rooting was achieved in 75.4% of shoots treated with 1476 μM indole-3-butyric acid (IBA) across all tested substrates. The plantlets subsequently acclimatized with a survival rate between 77.1% and 83.3%.
Analysis of Protein Inhibitors of Trypsin in Quinoa, Amaranth and Lupine Seeds. Selection and Deep Structure–Function Characterization of the Amaranthus caudatus Species
Authors: Hernández de la Torre Martha , Covaleda-Cortés Giovanni , Montesinos Laura , Covaleda Daniela , Ortiz Juan C. , Piñol Jaume , Bautista José M. , Castillo J. Patricio , Reverter David , Avilés Francesc Xavier
Published: January 2025

Protease inhibitors are biomolecules with growing biotechnological and biomedical relevance, including those derived from plants. This study investigated strong trypsin inhibitors in quinoa, amaranth, and lupine seeds, plant grains traditionally used in Andean South America. Amaranth seeds displayed the highest trypsin inhibitory activity, despite having the lowest content of aqueous soluble and thermostable protein material. This activity, directly identified by enzymatic assay, HPLC, intensity-fading mass spectrometry (IF-MS), and MS/MS, was attributed to a single protein of 7889.1 Da, identified as identical in Amaranthus caudatus and A. hybridus, with a Ki of 1.2 nM for the canonical bovine trypsin. This form of the inhibitor, which is highly homogeneous and scalable, was selected, purified, and structurally–functionally characterized due to the high nutritional quality of amaranth seeds as well as its promising agriculture–biotech–biomed applicability. The protein was crystallized in complex with bovine trypsin, and its 3D crystal structure resolved at 2.85 Å, revealing a substrate-like transition state interaction. This verified its classification within the potato I inhibitor family. It also evidenced that the single disulfide bond of the inhibitor constrains its binding loop, which is a key feature. Cell culture assays showed that the inhibitor did not affect the growth of distinct plant microbial pathogen models, including diverse bacteria, fungi, and parasite models, such as Mycoplasma genitalium and Plasmodium falciparum. These findings disfavour the notion that the inhibitor plays an antimicrobial role, favouring its potential as an agricultural insect deterrent and prompting a redirection of its functional research.
NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles
Authors: Naito Maiko , Takeda Yoshito , Edahiro Ryuya , Shirai Yuya , Enomoto Takatoshi , Nakayama Mana , Nojima Satoshi , Nogami-Ito Mari , Mori Masahide , Yano Yukihiro , Matsuki Takanori , Yoshimura Hanako , Hara Reina , Yamamoto Makoto , Masuhiro Kentaro , Naito Yujiro , Koyama Shohei , Iwahori Kota , Nagatomo Izumi , Shiroyama Takayuki , Miyake Kotaro , Hirata Haruhiko , Hase Hiroaki , Tsujikawa Kazutake , Ueda Koji , Kumanogoh Atsushi
Published: January 2025

Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by Mycobacterium avium complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made by sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on serum extracellular vesicles (EVs) collected from 10 patients with MAC pulmonary disease (MAC-PD), 7 patients with TB, and 10 healthy controls. A total of 2614 proteins were identified in the discovery cohort. The EV protein signature from patients with NTM-PD and TB reflected infectious diseases and inflammatory response pathways. Among the identified proteins, the expression of Na+/H+ exchanger regulatory factor 2 (NHERF2) was significantly elevated in patients with MAC-PD compared with healthy controls and patients with TB. Moreover, upregulation of NHERF2 was confirmed by immunoblotting of serum EVs and immunohistochemistry of lungs with mycobacterial infection. Our findings highlight that NHERF2 in serum EVs might be a potential biomarker for distinguishing MAC-PD from TB, possibly reflecting the pathogenesis of MAC-PD.
The Establishment of Artificial RNA Cascade Circuits for Gene Regulation Based on Doxycycline-Induced Pre-mRNA Alternative Splicing
Authors: Dai Guimin , Cheng Jiawen , Liu Weiran , Yin Xueli , Zhang Yuanyuan
Published: January 2025

This study developed an artificial chimeric intron module with an RNA riboswitch and TetR aptamer that were integrated into essential gene exons. Doxycycline can modulate Pre-mRNA alternative splicing, modify the exon reading frame, and dynamically regulate gene expression. By shifting the aptamer 2 base pair within the switch, we unexpectedly obtained the “on-switch” CTM and “off-switch” C2ITetR>4A, which possess thoroughly contrasting regulatory functions. The CTM module can conditionally induce tumor cell apoptosis and regulate genes reversibly and sustainably following doxycycline induction. We integrated the C2ITetR>4A/CTM switches with the L7Ae/k-turn module to create an intron-spliced double-switched RNA cascade system. The system can both activate and inhibit the splicing mechanism utilizing the same ligand to minimize crosstalk among aptamer switching elements, control target gene leakage, and enhance the dynamic range of gene expression. We analyzed numerous factors affecting Pre-mRNA splicing to identify the optimal equilibrium point for switch regulation. This will enable precise predictions of dynamic regulatory efficiency and the rational design of genetic modules, thereby providing a valuable instrument for mammalian synthetic biology.
Analyzing the Biochemistry of Saliva: Flow, Total Protein, Amylase Enzymatic Activity, and Their Interconnections
Authors: Parraca Jose A. , Rubio-Zarapuz Alejandro , Tornero-Aguilera José Francisco , Clemente-Suárez Vicente Javier , Tomas-Carus Pablo , Costa Ana Rodrigues
Published: January 2025

This study examines the biochemical profile of saliva, focusing on flow rate, total protein concentration, and the enzymatic activities of amylase and catalase. The study aims to explore the correlations between these parameters and their response to physiological stress induced by physical activity, providing insights into saliva’s diagnostic potential. Thirty-one participants were recruited, and saliva samples were collected before and after a structured physical activity session. Biochemical parameters were analyzed using established protocols to assess changes induced by exercise. Significant positive correlations were observed between protein concentration and amylase activity, particularly in post-exercise conditions. No significant correlations were found between the salivary flow and enzyme activities. Catalase activity displayed a weaker association with protein levels. These findings suggest that saliva can be a non-invasive biomarker for systemic health and stress responses. The study highlights the diagnostic utility of saliva and underscores the need for further investigations in younger and healthier populations to broaden the applicability of these results.
Late Gadolinium Enhancement Magnetic Resonance Imaging (MRI) for Predicting Left Ventricular Reverse Remodeling in Non-Ischemic Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Teraoka Yuri , Kato Shingo , Yasuda Naofumi , Sawamura Shungo , Horita Nobuyuki , Utsunomiya Daisuke
Published: January 2025

Background/Objectives: Late gadolinium enhancement (LGE)-MRI has proven utility in prognosticating outcomes in patients with non-ischemic cardiomyopathy (NICM). However, evidence regarding its ability to predict responsiveness to optimal medical therapy remains insufficient. This study conducted a meta-analysis to evaluate the predictive utility of LGE-MRI for left ventricular reverse remodeling (LVRR) in response to pharmacological therapy. Methods: Data from 1092 NICM patients across 13 studies were included in the analysis. To assess the predictive ability of LGE-MRI for LVRR following optimal medical therapy, a pooled odds ratio was calculated using an inverse variance random-effects meta-analysis. Subgroup analyses were performed by stratifying patients based on the presence or absence of left ventricular dilation and by LVEF (<30% vs. ≥30%). Results: The pooled odds ratio of the absence of LGE for predicting LVRR in NICM was 3.72 (95% CI: 2.83–4.90, I2 = 0, P for heterogeneity = 0.54). A comparison of pooled odds ratios between dilated cardiomyopathy (DCM) and NICM showed no significant difference (p = 0.16). A subgroup analysis in NICM based on the left ventricular ejection fraction (LVEF) demonstrated no significant difference in odds ratios between patients with LVEF <30% (OR: 2.96, 95% CI: 1.80–4.87) and those with LVEF ≥30% (OR: 3.97, 95% CI: 2.97–5.31), (p = 0.13). Conclusions: This meta-analysis suggested that LGE-MRI serves as a reliable predictor of LVRR in patients with NICM, regardless of left ventricular dilation or baseline LVEF classification.
Pre-Clinical and Clinical Advances in Gene Therapy of X-Linked Retinitis Pigmentosa: Hope on the Horizon
Authors: Pechnikova Nadezhda A. , Poimenidou Malamati , Iliadis Ioannis , Zafeiriou-Chatziefraimidou Maria , Iaremenko Aleksandra V. , Yaremenko Tamara V. , Domvri Kalliopi , Yaremenko Alexey V.
Published: January 2025

X-linked retinitis pigmentosa (XLRP) is a severe inherited retinal degenerative disease characterized by progressive loss of photoreceptors and retinal pigment epithelium, leading to blindness. Predominantly affecting males due to mutations in the RPGR gene, XLRP currently lacks effective treatments beyond supportive care. Gene therapy has emerged as a promising approach to restore photoreceptor function by delivering functional copies of the RPGR gene. Recent clinical trials using AAV vectors, such as AAV5-RPGR and AGTC-501, have demonstrated encouraging results, including improvements in retinal sensitivity and visual function. While early successes like LUXTURNA have set the precedent for gene therapy in retinal diseases, adapting these strategies to XLRP presents unique challenges due to the complexity of RPGR mutations and the need for efficient photoreceptor targeting. Advances in vector design, including the use of optimized AAV serotypes with enhanced tropism for photoreceptors and specific promoters, have significantly improved gene delivery. Despite setbacks in some studies, ongoing research and clinical trials continue to refine these therapies, offering hope for patients affected by XLRP. This review explores the etiology and pathophysiology of XLRP, evaluates current treatment challenges, highlights recent clinical advances in gene therapy, and discusses future perspectives for bringing these therapies into clinical practice.
Sex-Specific Differences in Chronic Thromboembolic Pulmonary Hypertension Treated with Balloon Pulmonary Angioplasty
Authors: Kurzyna Paweł , Witowicz Anna , Kędzierski Piotr , Florczyk Michał , Banaszkiewicz Marta , Szwed Piotr , Piłka Michał , Gąsecka Aleksandra , Pietrasik Arkadiusz , Torbicki Adam , Kurzyna Marcin , Darocha Szymon
Published: January 2025

Background/Objectives: Several studies describe the sex-specific differences in cardiovascular diseases. However, there is still limited research reporting the difference between men and women with chronic thromboembolic pulmonary hypertension (CTEPH) treated with balloon pulmonary angioplasty (BPA). The aim of this study was to evaluate sex-specific differences in patients with CTEPH treated with BPA. Methods: This retrospective study included CTEPH patients treated with BPA. The patients’ hemodynamic and clinical parameters were assessed at baseline and 3 months after completion of BPA treatment. Results: This study included 94 patients (44 women, 46.8%). At baseline, women had higher systolic pulmonary arterial pressure (sPAP) (76 ± 18.5 vs. 85 ± 17.6 mmHg; p = 0.03) and pulmonary vascular resistance (8.21 [5.55–10.17] vs. 9.89 [6.31–14.06] Wood Units; p = 0.03) compared to men. There were no differences in clinical characteristics between the sexes. At follow-up, women had lower sPAP (49 [41–54] vs. 43 [37–49] mmHg; p = 0.04) and pulmonary capillary wedge pressure (10 [9–14] vs. 9 [8–11] mmHg; p = 0.03), but a higher cardiac index (2.57 ± 0.53 vs. 2.82 ± 0.50 L/min/m2; p = 0.03), as well as better Dyspnea Borg Scale outcomes, compared to men. Women had a greater reduction in mean pulmonary artery pressure (−43% vs. −37%; p = 0.049) than men. Conclusions: At baseline, women with CTEPH had worse hemodynamic parameters than men despite similar clinical symptoms. However, the hemodynamic status of women was better after BPA therapy. Hence, women seem better adapted to the disease at baseline and respond better to BPA. Further data are needed to investigate whether the management of CTEPH patients should be sex-differentiated.
Prognostic Value of Preoperative Albumin-to-Alkaline Phosphatase Ratio for Survival in Colorectal Cancer Patients Undergoing Surgery
Authors: Arak Hacı , Gumusburun Ercan , Seyyar Mustafa , Yesil Cinkir Havva
Published: January 2025

Background and Objectives: This study aimed to evaluate the prognostic significance of the pre-treatment albumin-to-alkaline phosphatase ratio (AAPR) in early-stage colorectal cancer patients and to compare it with the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the same patient cohort. Materials and Methods: This retrospective study included 540 patients who were followed up after a diagnosis of early-stage colorectal cancer and whose albumin (ALB), alkaline phosphatase (ALP), neutrophil, platelet, and lymphocyte values were measured before treatment. Results: In the receiver operating characteristic (ROC) curve analysis for overall survival (OS), the AAPR index Area Under Curve (AUC):0.560, (p = 0.018), NLR index (p = 0.079), and PLR index (p = 0.692) were evaluated. In the ROC analysis for OS, a cut-off value of the AAPR index of ≤0.423 was found. In the AAPR-low group, the relapse and death rates were higher than in the AAPR-high group (p = 0.004 and p = 0.001, respectively). As the AAPR index decreased, the NLR and PLR indexes increased (p = 0.027 and p = 0.003, respectively). Median disease-free survival (DFS) was worse in the AAPR-low group (128 versus 156) months (p = 0.015). The AAPR index significantly affected OS with hazard ratio (HR):0.42 (95%CI, 0.18–0.97) (p = 0.044). At 5 years, 68% of the patients in the AAPR-low group and 79% of the patients in the AAPR-high group were alive (p = 0.005). In a multivariate analysis, low AAPR, patient age at diagnosis, TNM stage, and recurrence status were independent factors affecting OS (p = 0.022, p < 0.001, p = 0.002, and p < 0.001, respectively). Conclusions: In early-stage colorectal cancer patients, the OS was worse in the AAPR-low group than in the AAPR-high group. The AAPR index demonstrated significant prognostic value for OS compared to the NLR and PLR in the same patient cohort.
Development and Characterization of a Gelatin-Based Photoactive Hydrogel for Biomedical Application
Authors: Straksys Antanas , Abouhagger Adei , Kirsnytė-Šniokė Monika , Kavleiskaja Tatjana , Stirke Arunas , Melo Wanessa C. M. A.
Published: January 2025

Photoactive hydrogels facilitate light-triggered photochemical processes, positioning them as innovative solutions in biomedical applications, especially in antimicrobial photodynamic therapy. This study presents a novel methylene blue-based photoactive hydrogel designed as a topical gel solution to overcome the limitations of traditional pad-based systems by offering enhanced adaptability to irregular wound surfaces, uniform photosensitizer distribution, and deeper therapeutic light penetration. This study investigated the development of hydrogels by cross-linking gelatin with glutaraldehyde (GA) and incorporating methylene blue (MB) to investigate the effects of cross-linking density, network structure, and small molecule inclusion on hydrogel properties. The results showed that while glutaraldehyde concentration influenced swelling behavior and network structure, the inclusion of MB altered these properties, particularly reducing swelling and MB retention at higher GA concentrations. Rheological and thermal analyses confirmed that higher GA concentrations made the hydrogels more rigid, with MB influencing both mechanical and thermal properties. Additionally, the hydrogels exhibited enhanced antimicrobial properties through increased reactive oxygen species production, particularly in light-activated conditions, demonstrating the potential of MB-based photoactive hydrogels for improving antimicrobial efficacy, especially against S. aureus, E. coli, and C. albicans, offering as a possible alternative to traditional antimicrobial treatments.
Reconfigurable Manufacturing Systems: Enhancing Efficiency via Product Family Optimization
Authors: Chaymae Bahtat , Abdellah El Barkany
Published: January 2025

In response to the increasing complexity of modern production environments driven by heightened competition, customer demands, and sustainability goals, this work presents a focused methodology for forming product families within reconfigurable manufacturing systems (RMSs). Unlike traditional approaches, our method emphasizes the practical implementation of the Analytic Hierarchy Process (AHP) and the Average Linkage Clustering (ALC) algorithm to optimize RMS configurations. By evaluating specific comparison criteria—such as assembly sequence, machining sequence, components, production tools, and production demand—we aim to enhance resource utilization and adaptability to market changes. The proposed methodology enables a systematic assessment of RMS performance tailored to diverse product requirements. A detailed example of machining systems demonstrates the use of machining sequence and tool usage as primary criteria, showcasing the practical application and decision-making capabilities of the approach. This work contributes to the field by providing a structured framework for decision-making in RMS, facilitating efficient and precise product family formation to meet evolving manufacturing demands.
Erythema Nodosum Associated with Kerion: A Case Series and Narrative Review of the Literature
Authors: Rattananukrom Teerapong , Uh-Sánchez Isaías , Atoche-Dieguez Carlos , Eljure Nixma , Garcia-Rementeria Carlos , Arenas Roberto
Published: January 2025

Kerion is a form of inflammatory tinea capitis, a fungal infection caused by various zoophilic, geophilic, and anthropophilic pathogens. Erythema nodosum (EN), a form of septal panniculitis, can be considered a dermatophyte id reaction that occurs outside the primary site of dermatophyte infection. The association between EN and kerion is rarely reported, with most cases following Trichophyton mentagrophytes scalp infections. Here, we describe three cases of EN associated with kerion caused by T. mentagrophytes, successfully treated with itraconazole or griseofulvin plus prednisone. Additionally, we conducted a narrative review of the literature, identifying 23 reported cases of EN associated with kerion on PubMed. The most commonly reported fungus was T. mentagrophytes (78.25%). In 52.17% of cases, patients developed EN after initiating antifungal treatment, with a mean onset time of 11.58 days (SD 7.3). Griseofulvin remains a mainstay treatment. The mean time for EN resolution was 8.31 days (SD 4.15), and the median duration of treatment for kerion leading to a complete response was 6 weeks (IQR 6–8). Scarring alopecia is a common sequela following kerion, and the use of corticosteroids has been recommended as adjunct therapy to minimize the risk of scarring.
Selection and Timing Skill in Bond Mutual Fund Returns: Evidence from Bootstrap Simulations
Authors: Huang Lifa , Lee Wayne Y. , Rennie Craig G.
Published: January 2025

We show that U.S. open-end actively managed domestic bond mutual fund managers possess selection and short-term timing skills based on monthly returns from 1999 to 2016. Parametric tests bias against finding evidence of manager skill, and correction for precision of alpha matters most when true alpha is uncertain. Our bootstrap simulations use precision-adjusted alpha (t(α)) controlling for luck without relying on parametric statistics. We find: the top 50 percent of bond mutual fund managers generate positive precision-adjusted alpha net of expense; selection skill contributes to long-term fund performance; and timing skill adds to short-term fund results, especially for government bond funds compared to corporate bond funds.
Bacterial Communities from the Copper Mine of Wettelrode (Germany)
Authors: Köhler J. Michael , Ehrhardt Linda , Günther P. Mike , Cao Jialan
Published: January 2025

Bacterial communities from three different sampling sites of a copper mine tunnel were characterized by 16S rRNA sequencing (NGS). A high presence of halophilic bacteria was confirmed by comparison with literature data and with reference samples from other highly salt-exposed soils. Among others, high read numbers of Gracilimonas, Kangiella, Limibacillus, Marinobacter, Woseia, and uncultivated strains of Actinomarinales, Gammaproteobacterium AT-s16, Actinobacteria 0319-7L14, and Thiotrichaceae were found. The community in a sample from the surface of the copper seam was significantly different from the community composition of a sample from the mine tunnel floor. The specificity in the appearance and in the abundance of special bacterial types (for example, Thiogranum, Thiohalophilus, Sulfuriflexus, Sedimenticolaceae, Desulfomonile, Desulfosporosinus, and Cand. Thiobios) can be partially explained by the different local conditions for sulfur-related metabolisms at the sampling sites.