bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning Spatial Configuration Feature for Landmark Localization in Hand X-rays
Authors: Ham Gyu-Sung , Oh Kanghan
Published: September 2023

Medical landmark localization is crucial for treatment planning. Although FCN-based heatmap regression methods have made significant progress, there is a lack of FCN-based research focused on features that can learn spatial configuration between medical landmarks, notwithstanding the well-structured patterns of these landmarks. In this paper, we propose a novel spatial-configuration-feature-based network that effectively learns the anatomical correlation between the landmarks. Specifically, we focus on a regularization method and a spatial configuration loss that capture the spatial relationship between the landmarks. Each heatmap, generated using U-Net, is transformed into an embedded spatial feature vector using the soft-argmax method and spatial feature maps, here, Cartesian and Polar coordinates. A correlation map between landmarks based on the spatial feature vector is generated and used to calculate the loss, along with the heatmap output. This approach adopts an end-to-end learning approach, requiring only a single feedforward execution during the test phase to localize all landmarks. The proposed regularization method is computationally efficient, differentiable, and highly parallelizable. The experimental results show that our method can learn global contextual features between landmarks and achieve state-of-the-art performance. Our method is expected to significantly improve localization accuracy when applied to healthcare systems that require accurate medical landmark localization.
Downsizing Sustainable Aviation Fuel Production with Additive Manufacturing—An Experimental Study on a 3D printed Reactor for Fischer-Tropsch Synthesis
Authors: Metzger David F. , Klahn Christoph , Dittmeyer Roland
Published: September 2023

Sustainable aviation fuels (SAF) are needed in large quantities to reduce the negative impact of flying on the climate. So-called power-to-liquid (PtL) plants can produce SAF from renewable electricity, water, and carbon dioxide. Reactors for these processes that are suitable for flexible operation are difficult to manufacture. Metal 3D printing, also known as additive manufacturing (AM), enables the fabrication of process equipment, such as chemical reactors, with highly optimized functions. In this publication, we present an AM reactor design and conduct experiments for Fischer-Tropsch synthesis (FTS) under challenging conditions. The design includes heating, cooling, and sensing, among others, and can be easily fabricated without welding. We confirm that our reactor has excellent temperature control and high productivity of FTS products up to 800 kgC5+ mcat−3 h−1 (mass flow rate of hydrocarbons, liquid or solid at ambient conditions, per catalyst volume). The typical space-time yield for conventional multi-tubular Fischer-Tropsch reactors is ~100 kgC5+ mcat−3 h−1. The increased productivity is achieved by designing reactor structures in which the channels for catalyst and cooling/heating fluid are in the millimeter range. With the effective control of heat release, we observe neither the formation of hot spots nor catalyst deactivation.
Cleaner Cooking with Charcoal in Kibera Informal Settlement in Nairobi, Kenya, and Its Implications for Livelihoods and the Environment
Authors: Kirimi Moses , Gitau James K. , Mendum Ruth , Muthuri Catherine , Njenga Mary
Published: September 2023

Woodfuel that is unsustainably sourced and inefficiently used results in negative environmental and health impacts. This study assessed charcoal use and resultant concentrations of indoor air pollutants (IAP) in an urban informal settlement while cooking with a Jikokoa stove (an improved branded charcoal stove) and medium and small-sized artisanal Kenya Ceramic Jikos (KCJs). Fuel stacking was prevalent with charcoal and kerosene being used by 25% of the studied households. Cooking with a Jikokoa stove reduced charcoal consumption by 6.4% and 26% compared to small and medium-sized KCJs, respectively. The small-sized KCJ reduced charcoal consumption by 21% compared to the medium-sized KCJ. The Jikokoa stove reduced concentrations of carbon monoxide (CO) by 10% and 50% and fine particulate matter (PM2.5) by 6% and 77% compared to small-sized and medium-sized KCJs, respectively. The Jikokoa stove reduced carbon dioxide (CO2) concentrations by 15.6% compared to the medium-sized KCJ. The small-sized KCJ reduced CO and PM2.5 concentrations by 45% and 75%, respectively, compared to the medium-sized KCJ. In summary, small-sized KCJs are more effective than medium-sized ones, and Jikokoa stoves more effective than small-sized KCJs, making it the stove of choice. The more efficient charcoal stoves are, the more charcoal consumption and IAP can be reduced, mitigating environmental degradation, climate change and health problems associated with smoke in the kitchen. There is need for participatory research to scale improved stoves and upgrade local practices as they are cheaper and already embedded in the cooking culture.
The Green Effects of Industrial Policy—Evidence from China’s New Energy Vehicle Subsidies
Authors: Cai Qian , Ji Zheng , Ma Fuxun , Liang Han
Published: September 2023

The development of new energy vehicles has become a common choice for countries worldwide to reduce greenhouse gas emissions and improve the global ecological environment, with China being no exception. However, challenges, such as finding charging stations, accessing residential areas, and highway charging, have hindered the green and high-quality growth of the new energy vehicle industry. This study, set against the backdrop of China’s 2018 policy to gradually redirect local purchase subsidy funds for new energy vehicles towards supporting the construction and operation of charging infrastructure, utilizes panel data from 282 prefecture-level cities from 2016 to 2021. A difference-in-differences model is constructed to compare the impact of infrastructure development on carbon emissions before and after the policy’s implementation. The study finds that policy has a negative effect on carbon emissions, especially in the second and third year after the policy’s implementation. Even after controlling for variables such as residents’ wealth levels, population size, environmental pollution, energy consumption, and government support, the results remain significant. Heterogeneity analysis reveals that the effect of the promotion of charging infrastructure on carbon emissions is greater in southern and central parts of China.
Effect of Magnetic Shunts on Shell-Type Transformers Characteristics
Authors: Tomczuk Bronisław , Weber Dawid
Published: September 2023

A three-dimensional analysis of the leakage magnetic field in a transformer with beveled edges in a magnetic shunt is described. This paper contains a mathematical description of the finite element method used in performing numerical calculations. Formulas allowing to determine the differential and integral parameters of the magnetic field were presented. Magnetic flux density distributions and the points with high values were determined in the shell-type core and movable shunt sub-areas. For different positions of the magnetic shunt, the short-circuit transformer reactance was calculated as the integral parameter of the above-mentioned magnetic field analysis. Their amounts for the extreme positions of the shunt were given, as well. The movable magnetic shunt geometry impact on the short-circuit current value is given. In order to validate the calculation results, the research included some point measurements of magnetic flux density vectors and the winding reactances as well, and good compliance with the simulation data has been obtained. Thus, this analysis can also be applied to other objects with movable shunts in their magnetic systems.
Free Surface Motion of a Liquid Pool with Isothermal Sidewalls as a Benchmark for Marangoni Convection Problems
Authors: Ciccotosto Bruce E. , Brooks Caleb S.
Published: September 2023

In single phase flows, benchmarks like the lid driven cavity have become recognized as fundamental tests for newly developed computational fluid dynamics, CFD, codes. For multiphase free surface flows with variable surface tension, the presently studied pool with isothermal sidewalls is suggested as it is the simplest domain where Marangoni effects can dominate. It was also chosen due to its strange sensitivity to the initial setup which is discussed at length from a chosen number of ‘scenarios’. It was found that the fluid interface can reverse deformation by a change in the top boundary condition, the liquid equation of state, and the gravity level. For the top boundary condition, this reversal is due to vapor expansion within the closed volume, creating an additional convection mechanism. Not only does the interface reverse, but the peak height changes by more than an order of magnitude at the same Marangoni number. When including gravity, the peak velocity can increase significantly, but it can also cause a decrease when done in combination with a change in the top wall boundary condition. Finally, thermal expansion of the liquid phase causes the peak velocity to be reduced, with additional reductions from the gravity and top wall condition. The differences in each scenario could lead to significant errors in analyzing a practical application of Marangoni flows. Therefore, it is important to demonstrate that a new CFD code can not only resolve Marangoni convection, but also has the capability to resolve the scenario most relevant to the application at hand.
Low-Cost and High-Strength Soybean Meal Adhesives Modified by Tannin–Phenol–Formaldehyde Resin
Authors: Li Hanyin , Gao Yan , Zhao Zijie , Yang Fan , Zou Yunming , Wang Yujie , Tang Yang , Zhou Qiongqiong , Li Cheng
Published: September 2023

Wood adhesive is very important to the quality of wood-based panels in the forest product industry. Researchers are currently focused on developing green and environmentally friendly adhesives using biomass materials. Soybean meal (SM), a cheap and high-protein byproduct from soybean processing, is considered a green biomaterial resource for adhesive production. In this study, SM was modified using urea and sodium hydroxide as denaturants, and two cross-linking agents were prepared to incorporate into the soybean meal adhesive for bonding reactions. Sodium hydroxide added to soybean protein caused structural damage to the protein structure, which allowed the peptide chains to unfold extensively, forming a low-molecular-weight peptide mixture with a good size distribution and exposing numerous active functional groups for cross-linking with the tannin–phenol–formaldehyde resin (TR) and wood. Adding the epoxy resin CA and TR enabled the cross-linking agents to react with the active functional groups on proteins, forming a cross-linked network structure. As a result, the adhesive’s strength, residual rate, and solid content were improved.
Dead Better than Alive—The Case of Retention Trees and Tree-Related Microhabitats in Young Stands of Hemiboreal Forests in Latvia
Authors: Jansone Diāna , Matisons Roberts , Gerra-Inohosa Linda , Lībiete Zane , Jansons Āris
Published: September 2023

This study examines microhabitat abundance and composition on retention trees in 20 young stands in Latvia that were clear-cut between 2002 and 2004. Retention trees play a vital role in sustaining biological diversity after clear-cutting, but their mortality rate is often high due to post-harvest environmental changes. This study compares tree-related microhabitat (TreM) abundance and composition on retention trees of different dimensions, species, and vitality. The tree height and diameter were measured, and the living status and position of each tree were determined. The research questions of the study were to assess the relationships between TreMs, tree dimensions, and species, as well as to compare the occurrence of TreMs on living and dead wood. The comprehensive analysis revealed that larger tree diameters and specific tree species (Populus tremula, Fraxinus excelsior, and Salix caprea) lead to a higher abundance of TreMs. The results also highlighted the importance of preserving deadwood within forest stands as it enhances the observed abundance of TreMs. This study provides the missing information on TreMs in Latvia, thus providing data for comparison in a wider region.
Characteristics of Vegetation Change and Its Climatic and Anthropogenic Driven Pattern in the Qilian Mountains
Authors: Teng Yanmin , Wang Chao , Wei Xiaoqing , Su Meirong , Zhan Jinyan , Wen Lixiang
Published: September 2023

The Qilian Mountains (QLM) are an essential ecological security barrier in northwest China. Identifying the driven pattern of vegetation change is crucial for ecological protection and restoration in the QLM. Based on high-resolution vegetation coverage (VC) data in the QLM from 1990 to 2018, linear trend analysis was employed to examine the spatiotemporal dynamics of VC in the QLM, while correlation analysis was utilized to establish relationships between VC change and environmental factors. Multiple correlation analysis and residual analysis were adopted to recognize the climatically and anthropogenically driven pattern of VC change. The results showed that VC in the QLM presented a remarkable upward trend in volatility from 1990 to 2018. The significant increase areas accounted for 59.32% of the total, mainly distributed in the central and western QLM, and the significant decrease areas accounted for 9.18%, mostly located in the middle and eastern QLM. VC change showed a significant positive correlation with precipitation change and annual average temperature, while it exhibited a significant negative correlation with annual average precipitation, current VC status, livestock density, and slope. Climate change played a leading role in the increase of VC, and the impact of precipitation was significantly higher than that of temperature. Affected by climate change, the VC of alpine steppes and temperate steppes increased the most. Under the human interference, VC decreased significantly in 9.2% of the region, of which shrubs fell the most, followed by alpine meadows and forests. This study can provide certain guidance for local ecological protection and restoration efforts.
Visible and Infrared Image Fusion of Forest Fire Scenes Based on Generative Adversarial Networks with Multi-Classification and Multi-Level Constraints
Authors: Jin Qi , Tan Sanqing , Zhang Gui , Yang Zhigao , Wen Yijun , Xiao Huashun , Wu Xin
Published: September 2023

Aimed at addressing deficiencies in existing image fusion methods, this paper proposed a multi-level and multi-classification generative adversarial network (GAN)-based method (MMGAN) for fusing visible and infrared images of forest fire scenes (the surroundings of firefighters), which solves the problem that GANs tend to ignore visible contrast ratio information and detailed infrared texture information. The study was based on real-time visible and infrared image data acquired by visible and infrared binocular cameras on forest firefighters’ helmets. We improved the GAN by, on the one hand, splitting the input channels of the generator into gradient and contrast ratio paths, increasing the depth of convolutional layers, and improving the extraction capability of shallow networks. On the other hand, we designed a discriminator using a multi-classification constraint structure and trained it against the generator in a continuous and adversarial manner to supervise the generator, generating better-quality fused images. Our results indicated that compared to mainstream infrared and visible image fusion methods, including anisotropic diffusion fusion (ADF), guided filtering fusion (GFF), convolutional neural networks (CNN), FusionGAN, and dual-discriminator conditional GAN (DDcGAN), the MMGAN model was overall optimal and had the best visual effect when applied to image fusions of forest fire surroundings. Five of the six objective metrics were optimal, and one ranked second-to-optimal. The image fusion speed was more than five times faster than that of the other methods. The MMGAN model significantly improved the quality of fused images of forest fire scenes, preserved the contrast ratio information of visible images and the detailed texture information of infrared images of forest fire scenes, and could accurately reflect information on forest fire scene surroundings.
Archaeal Tubulin-like Proteins Modify Cell Shape in Haloferax volcanii during Early Biofilm Development
Authors: Cooper Alexei , Makkay Andrea M. , Papke R. Thane
Published: September 2023

Tubulin, an extensively studied self-assembling protein, forms filaments in eukaryotic cells that affect cell shape, among other functions. The model archaeon Haloferax volcanii uses two tubulin-like proteins (FtsZ1/FtsZ2) for cell division, similar to bacteria, but has an additional six related tubulins called CetZ. One of them, CetZ1, was shown to play a role in cell shape. Typically, discoid and rod shapes are observed in planktonic growth, but under biofilm formation conditions (i.e., attached to a substratum), H. volcanii can grow filamentously. Here, we show that the deletion mutants of all eight tubulin-like genes significantly impacted morphology when cells were allowed to form a biofilm. ΔftsZ1, ΔcetZ2, and ΔcetZ4-6 created longer, less round cells than the parental and a higher percentage of filaments. ΔcetZ1 and ΔcetZ3 were significantly rounder than the parental, and ΔftsZ2 generated larger, flat, amorphic cells. The results show all tubulin homologs affect morphology at most timepoints, which therefore suggests these genes indeed have a function.
Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs
Authors: Yasmin  , O’Shaughnessy Kevin M.
Published: September 2023

Genome-wide scans performed in affected sib pairs have revealed small and often inconsistent clues to the loci responsible for the inherited components of hypertension. Since blood pressure is a quantitative trait regulated by many loci, two siblings at opposite extremes of the blood pressure distribution are more likely to have inherited different alleles at any given locus. Hence, we investigated an extreme discordant sib pair strategy to analyse markers from two previous loci of interest: (1) the Gordons syndrome locus that includes the WNK4 gene and (2) the ROMK locus identified in our first genome-wide scan. For this study, 24 sib pairs with strong family histories of essential hypertension were selected from the top and bottom 10% of the blood pressure distribution and genotyped for highly polymorphic microsatellite markers on chromosomes 11 and 17. The mean age of the population was 39.8 ± 7.8 years. A significant inverse correlation was found between the squared difference in pulse pressure and the number of alleles shared by IBD between the siblings for the DS11925 marker (r = −0.44, p = 0.031), systolic pressure and chromosome 17 markers (D17S250: r = −0.42, p = 0.040; D17S799 (r = −0.51, p = 0.011), and this relationship persisted after correcting for age and gender. Markers on chromosome 17 (D17S250, D17S928 and D17S1301) and 11 (D11S1999) also correlated with diastolic pressure. These results illustrate the successful use of discordant sib pair analysis to detect linkage within relatively small numbers of pedigrees with hypertension. Further analysis of this cohort may be valuable in complementing findings from the large genome wide scans in affected sib pairs.
Molecular Evolution and Protein Structure Variation of Dkk Family
Authors: Wen Binhong , Hu Sile , Yin Jun , Wu Jianghong , Guo Wenrui
Published: September 2023

Dkks have inhibitory effects on the Wnt signaling pathway, which is involved in the development of skin and its appendages and the regulation of hair growth. The nucleotide sequences were compared and analyzed to further investigate the relationship between the structure and function of the Dkk gene family and vertebrate epidermal hair. The analysis of the molecular evolution of the Dkk family revealed that the evolution rate of the genes changed significantly after speciation, with the Aves and Reptilia branches showing accelerated evolution. Additionally, positive selection was observed at specific sites. The tertiary structure of the protein was also predicted. The analysis of the functional divergence of the Dkk family revealed that the functional divergence coefficient of each gene was greater than 0, with most of the functional divergence sites were located in the Cys-2 domain and a few in the Cys-1 domain. This suggests that the amino acid and functional divergence sites may play a role in regulating the binding of the Dkk family to LRP5/6, and thus affect the inhibition of Wnt signaling, leading to different functions of Dkk1, Dkk2, and Dkk4 in the development of skin hair follicles. In addition, the Dkk families of Aves and Reptilia may have undergone adaptive evolution and functional divergence.
Complete Mitochondrial Genome Characterization of Schrankia costaestrigalis (Insecta: Erebidae: Hypenodinae) and Its Phylogenetic Implication
Authors: Gao Xuyuan , Bai Yu , Jiang Xiaodong , Long Xiuzhen , Wei Dewei , He Zhan , Zeng Xianru , Yu Yonghao
Published: September 2023

The pinion-streaked snout Schrankia costaestrigalis is a new potato pest that has recently been recorded in China. In this study, we analyzed the complete mitochondrial genome of S. costaestrigalis. The results revealed the mitogenome (GenBank: OQ181231) to occur as a circular DNA molecule of 16,376 bp with 51.001% AT content, including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 1 control region. Notably, the PCGs exhibited typical ATN (Met) start codons, including cox1, which deviated from the usual CGA start codon observed in other lepidopteran mitogenomes, and followed the conventional TAN stop codons. The 22 tRNA genes demonstrated the ability to form a cloverleaf structure, with the exception of trnS1-NCU, which lacked the DHU arm present in other Erebidae mitogenomes. Additionally, conserved motifs like “ATAGA + poly-T (19 bp) stretch” and five microsatellite-like elements (TA) were identified in the AT-rich region. The phylogenetic trees revealed that the Hypenodinae subfamily forms an independent lineage closely related to Erebinae and Catocalinae. The comprehensive mitogenome of S. costaestrigalis will greatly enhance future studies focused on the molecular classification and phylogenetic understanding of the Hypenodinae subfamily within the larger family Erebidae.
The Influence of Short-Term Weather Parameters and Air Pollution on Adolescent Airway Inflammation
Authors: Areal Ashtyn Tracey , Singh Nidhi , Zhao Qi , Berdel Dietrich , Koletzko Sibylle , von Berg Andrea , Gappa Monika , Heinrich Joachim , Standl Marie , Abramson Michael J. , Schikowski Tamara
Published: September 2023

Fraction of exhaled Nitric Oxide (FeNO) is a marker of airway inflammation. We examined the main effects and interactions of relative humidity (RH) and air pollution on adolescents’ FeNO. Two thousand and forty-two participants from the 15-year follow-up of the German GINIplus and LISA birth cohorts were included. Daily meteorological (maximum [Tmax], minimum [Tmin] and mean [Tmean] temperatures and RH) and air pollution [Ozone (O3), nitrogen dioxide (NO2) and particulate matter < 2.5 µm (PM2.5)] were assessed. Linear models were fitted with Ln(FeNO) as the outcome. Increases in FeNO indicate an increase in lung inflammation. Increased FeNO was associated with an increase in temperature, PM2.5, O3 and NO2. A 5% increase in RH was associated with a decrease in FeNO. Interactions between RH and high (p = 0.007) and medium (p = 0.050) NO2 were associated with increases in FeNO; while interactions between RH and high (p = 0.042) and medium (p = 0.040) O3 were associated with decreases in FeNO. Adverse effects were present for male participants, participants with low SES, participants with chronic respiratory disease, and participants from Wesel. Short-term weather and air pollution have an effect on lung inflammation in German adolescents. Future research should focus on further assessing the short-term effect of multiple exposures on lung inflammation in adolescents.
Current Trends in Balance Rehabilitation for Stroke Survivors: A Scoping Review of Experimental Studies
Authors: Saraiva Júlia , Rosa Gonçalo , Fernandes Sónia , Fernandes Júlio Belo
Published: September 2023

Balance impairment is a common consequence of a stroke, which can significantly hinder individuals’ participation in daily activities, social interactions, and leisure pursuits and their ability to return to work. Rehabilitation is vital for minimizing post-stroke sequelae and facilitating the recovery of patients. This review aims to identify current trends in balance rehabilitation of stroke survivors. This Scoping review followed Arksey and O’Malley’s methodological framework. The literature search was conducted in electronic databases, including CINAHL Complete, MEDLINE Complete, and Nursing & Allied Health Collection. The search was performed in March 2023, and the inclusion criteria were articles published in English or Portuguese between 2013 and 2023. A total of 446 articles were identified. After selecting and analyzing the reports, fourteen publications were included in this review. Seven distinct categories of balance rehabilitation interventions were identified, covering various approaches. These categories included conventional rehabilitation exercises, gym-based interventions, vibration therapy, rhythmic auditory stimulation training, boxing therapy, dual-task training, and technology-based rehabilitation interventions. Each of these methods presents unique benefits and can significantly impact the recovery of balance in stroke survivors, enhancing their overall well-being and functional capacity.
Housing Instability Associated with Return to Stimulant Use among Previously Abstaining Women
Authors: Mehtani Nicky J. , Chuku Chika C. , Meacham Meredith C. , Vittinghoff Eric , Dilworth Samantha E. , Riley Elise D.
Published: September 2023

Stimulant use among unstably housed individuals is associated with increased risks of psychiatric co-morbidity, violence, HIV transmission, and overdose. Due to a lack of highly effective treatments, evidence-based policies targeting the prevention of stimulant use disorder are of critical importance. However, little empirical evidence exists on risks associated with initiating or returning to stimulant use among at-risk populations. In a longitudinal cohort of unstably housed women in San Francisco (2016–2019), self-reported data on stimulant use, housing status, and mental health were collected monthly for up to 6 months, and factors associated with initiating stimulants after a period of non-use were identified through logistic regression. Among 245 participants, 42 (17.1%) started using cocaine and 46 (18.8%) started using methamphetamine. In analyses adjusting for demographics and socio-structural exposures over the preceding month, experiencing street homelessness was associated with initiating cocaine use (AOR: 2.10; 95% CI: 1.04, 4.25) and sheltered homelessness with initiating methamphetamine use (AOR: 2.57; 95% CI: 1.37, 4.79). Other factors—including race, income, unmet subsistence needs, mental health, and treatment adherence—did not reach levels of significance, suggesting the paramount importance of policies directed toward improving access to permanent supportive housing to prevent stimulant use among unstably housed women.
Validation and Psychometric Properties of the German Operational and Organizational Police Stress Questionnaires
Authors: Willemin-Petignat Lauriane , Anders Royce , Ogi Sabrina , Putois Benjamin
Published: September 2023

Context: Working in the police force is an operationally and organizationally stressful job. Suitable psychometric tools are needed to detect and study the psychosocial risks of these professionals. The original version contains 40 items, which may be too long for clinical use or as a research control measure. The main aim of this study is to validate the Police Stress Questionnaire (PSQ) in German. The secondary objective is to validate a shorter version. Method: After translation and counter translation of the PSQ-G by a committee of experts, 10 participants pre-tested the comprehension of an intermediate version, allowing the development of a final version that was submitted to a psychometric validation plan with 2314 German-speaking officers. Structure, reliability, and convergent, divergent, and discriminant validities were tested for each sample. Results: The German version of the PSQ performed well psychometrically. We have created a short version of 14 items with good psychometric properties, 7 items for each subscale: operational stressors and organizational stressors. Conclusion: This study validated a German version of the PSQ and provides a reliable measure of stress processes in the police force. A short version is now available.
Analyzing Current Trends and Possible Strategies to Improve Sucrose Isomerases’ Thermostability
Authors: Sardiña-Peña Amado Javier , Mesa-Ramos Liber , Iglesias-Figueroa Blanca Flor , Ballinas-Casarrubias Lourdes , Siqueiros-Cendón Tania Samanta , Espinoza-Sánchez Edward Alexander , Flores-Holguín Norma Rosario , Arévalo-Gallegos Sigifredo , Rascón-Cruz Quintín
Published: September 2023

Due to their ability to produce isomaltulose, sucrose isomerases are enzymes that have caught the attention of researchers and entrepreneurs since the 1950s. However, their low activity and stability at temperatures above 40 °C have been a bottleneck for their industrial application. Specifically, the instability of these enzymes has been a challenge when it comes to their use for the synthesis and manufacturing of chemicals on a practical scale. This is because industrial processes often require biocatalysts that can withstand harsh reaction conditions, like high temperatures. Since the 1980s, there have been significant advancements in the thermal stabilization engineering of enzymes. Based on the literature from the past few decades and the latest achievements in protein engineering, this article systematically describes the strategies used to enhance the thermal stability of sucrose isomerases. Additionally, from a theoretical perspective, we discuss other potential mechanisms that could be used for this purpose.
Mathematical Modeling Support for Lung Cancer Therapy—A Short Review
Authors: Smieja Jaroslaw
Published: September 2023

The paper presents a review of models that can be used to describe dynamics of lung cancer growth and its response to treatment at both cell population and intracellular processes levels. To address the latter, models of signaling pathways associated with cellular responses to treatment are overviewed. First, treatment options for lung cancer are discussed, and main signaling pathways and regulatory networks are briefly reviewed. Then, approaches used to model specific therapies are discussed. Following that, models of intracellular processes that are crucial in responses to therapies are presented. The paper is concluded with a discussion of the applicability of the presented approaches in the context of lung cancer.
Investigating the Effect of Surface Hydrophilicity on the Destiny of PLGA-Poloxamer Nanoparticles in an In Vivo Animal Model
Authors: Silvestri Teresa , Grumetto Lucia , Neri Ilaria , De Falco Maria , Graziano Sossio Fabio , Damiano Sara , Giaquinto Daniela , Maruccio Lucianna , de Girolamo Paolo , Villapiano Fabrizio , Ciarcia Roberto , Mayol Laura , Biondi Marco
Published: September 2023

This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.
Nuciferine Inhibits Oral Squamous Cell Carcinoma Partially through Suppressing the STAT3 Signaling Pathway
Authors: Xie Ji-Rong , Chen Xiao-Jie , Zhou Gang
Published: September 2023

Oral squamous cell carcinoma (OSCC) poses a significant obstacle to the worldwide healthcare system. Discovering efficient and non-toxic medications is crucial for managing OSCC. Nuciferine, an alkaloid with an aromatic ring, is present in the leaves of Nelumbo nucifera. It has been proven to play a role in multiple biological processes, including the inhibition of inflammation, regulation of the immune system, formation of osteoclasts, and suppression of tumors. Despite the demonstrated inhibitory effects of nuciferine on different types of cancer, there is still a need for further investigation into the therapeutic effects and potential mechanisms of nuciferine in OSCC. Through a series of in vitro experiments, it was confirmed that nuciferine hindered the growth, movement, and infiltration, while enhancing the programmed cell death of OSCC cells. Furthermore, the administration of nuciferine significantly suppressed the signal transducer and activator of transcription 3 (STAT3) signaling pathway in comparison to other signaling pathways. Moreover, the activation of the STAT3 signaling pathway by colivelin resulted in the reversal of nuciferine-suppressed OSCC behaviors. In vivo, we also showed the anti-OSCC impact of nuciferine using the cell-based xenograft (CDX) model in nude mice. Nonetheless, colivelin diminished the tumor-inhibiting impact of nuciferine, suggesting that nuciferine might partially impede the advancement of OSCC by suppressing the STAT3 signaling pathway. Overall, this research could offer a fresh alternative for the pharmaceutical management of OSCC.
The Diagnosis and Management of Cutaneous Metastases from Melanoma
Authors: Di Raimondo Cosimo , Lozzi Flavia , Di Domenico Pier Paolo , Campione Elena , Bianchi Luca
Published: September 2023

Melanoma is one of the deadliest skin tumors, accounting for almost 90% of skin cancer mortality. Although immune therapy and targeted therapy have dramatically changed the prognosis of metastatic melanoma, many patients experience disease progression despite the currently available new treatments. Skin metastases from melanoma represent a relatively common event as first sign of advanced disease or a sign of recurrence. Skin metastases are usually asymptomatic, although in advanced stages, they can present with ulceration, bleeding, and superinfection; furthermore, they can cause symptoms related to compression on nearby tissues. Treatments vary from simple surgery resections to topical or intralesional local injections, or a combination of these techniques with the most recent systemic immune or target therapies. New research and studies should focus on the pathogenesis and molecular mechanisms of the cutaneous metastases of melanoma in order to shed light on the mechanisms underlying the different behavior and prognoses of different patients.
NTHL1 Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
Authors: Grot Natalia , Kaczmarek-Ryś Marta , Lis-Tanaś Emilia , Kryszczyńska Alicja , Nowakowska Dorota , Jakubiuk-Tomaszuk Anna , Paszkowski Jacek , Banasiewicz Tomasz , Hryhorowicz Szymon , Pławski Andrzej
Published: September 2023

Multiple polyposes are heterogeneous diseases with different underlying molecular backgrounds, sharing a common symptom: the presence of transforming into cancerous intestinal polyps. Recent reports have indicated biallelic mutations in the NTHL1 gene, which is involved in base excision repair (BER), as predisposing to an elevated risk of colorectal cancer (CRC). We aimed to evaluate the significance of the p.Q82* truncating variant in predisposition to intestinal polyposis by assessing its frequency in polyposis patients. We genotyped 644 Polish patients and 634 control DNA samples using high-resolution melting analysis (HRM) and Sanger sequencing. We found the p.Q82* variant in four polyposis patients; in three, it was homozygous (OR = 6.90, p value = 0.202). Moreover, the p.R92C mutation was detected in one patient. We also looked more closely at the disease course in patients carrying NTHL1 mutations. Two homozygous patients also presented other neoplasia. In the family case, we noticed the earlier presence of polyps in the proband and early hepatoblastoma in his brother. We cannot univocally confirm the relationship of p.Q82* with an increased risk of CRC. However, homozygous p.Q82* was more frequent by 10-fold in patients without other mutations identified, which makes NTHL1 gene screening in this group reasonable.
A Novel tRNA-Derived Fragment, tRFGlnCTG, Regulates Angiogenesis by Targeting Antxr1 mRNA
Authors: Chen Qiuyang , Shen Linyuan , Liao Tianci , Qiu Yanhao , Lei Yuhang , Wang Xingyu , Chen Lei , Zhao Ye , Niu Lili , Wang Yan , Zhang Shunhua , Zhu Li , Gan Mailin
Published: September 2023

As a novel non-coding RNA with important functions corresponding to various cellular stresses, the function of tRFs in angiogenesis remains unclear. Firstly, small RNA sequencing was performed on normal and post-muscle injury mouse tibialis anterior muscle to identify and analyse differentially expressed tRF/tiRNA. tRNA GlnCTG-derived fragments (tRFGlnCTG) were found to be overexpressed in high abundance in the damaged muscle. Subsequent in vitro experiments revealed that the overexpression of tRFGlnCTG suppressed the vascular endothelial cells’ viability, cell cycle G1/S transition, proliferation, migration, and tube-formation capacity. Similarly, in vivo experiments showed that the tRFGlnCTG decreased the relative mRNA levels of vascular endothelial cell markers and pro-angiogenic factors and reduced the proportion of CD31-positive cells. Finally, luciferase activity analysis confirmed that the tRFGlnCTG directly targeted the 3′UTR of Antxr1, leading to a significant reduction in the mRNA expression of the target gene. These results suggest that tRFGlnCTG is a key regulator of vascular endothelial cell function. The results provide a new idea for further exploration of the molecular mechanisms that regulate angiogenesis.
Immune Activation and Inflammatory Response Mediated by the NOD/Toll-like Receptor Signaling Pathway—The Potential Mechanism of Bullfrog (Lithobates catesbeiana) Meningitis Caused by Elizabethkingia miricola
Authors: Li Fulong , Chen Baipeng , Xu Ming , Feng Yang , Deng Yongqiang , Huang Xiaoli , Geng Yi , Ouyang Ping , Chen Defang
Published: September 2023

Elizabethkingia miricola is an emerging opportunistic pathogen that is highly pathogenic in both immunocompromised humans and animals. Once the disease occurs, treatment can be very difficult. Therefore, a deep understanding of the pathological mechanism of Elizabethkingia miricola is the key to the prevention and control of the disease. In this study, we isolated the pathogenic bacteria from bullfrogs with dark skin color, weak limbs, wryneck, and cataracts. Via subsequent morphological observations and a 16S rRNA gene sequence analysis, the pathogen was identified as Elizabethkingia miricola. The histopathological and transmission electron microscopy analysis revealed that the brain was the main target organ. Therefore, brain samples from diseased and healthy bullfrogs were used for the RNA-Seq analysis. The comparative transcriptome analysis revealed that the diseased bullfrog brain was characterized by the immune activation and inflammatory response, which were mediated by the “NOD-like receptor signaling pathway” and the “Toll-like receptor signaling pathway”. We also performed qRT-PCR to examine the expression profile of inflammation-related genes, which further verified the reliability of our transcriptome data. Based on the above results, it was concluded that the NOD/Toll-like receptor-related networks that dominate the immune activation and inflammatory response were activated in the brain of Elizabethkingia miricola-infected bullfrogs. This study contributes to the search for therapeutic targets for bullfrog meningitis and provides basic information for establishing effective measures to prevent and control bullfrog meningitis.
Microbial Community Response to Various Types of Exogenous Organic Matter Applied to Soil
Authors: Siebielec Sylwia , Marzec-Grządziel Anna , Siebielec Grzegorz , Ukalska-Jaruga Aleksandra , Kozieł Monika , Gałązka Anna , Przybyś Marcin , Sugier Piotr , Urbaniak Magdalena
Published: September 2023

Recycling of solid biowaste and manure would reduce the dependence of agriculture on synthetic products. Most of the available studies on the effects of exogenous organic matter (EOM) application to soil were focused on nutrients and crop yield, with much less attention to microbiological processes in soil, especially using modern molecular methods. The aim of this study was to evaluate the effects of various types of manure, sewage sludge and bottom sediment on the biochemical activity and biodiversity of soil and plant yield in a pot experiment. The soil was treated with a range of EOM types: six types of manure (cattle, pig, goat, poultry, rabbit and horse manure; two bottom sediments (from urban and rural systems); and two types of municipal sewage sludge. All EOMs stimulated dehydrogenases activity at a rate of 20 t ha−1. Alkaline phosphatase was mostly stimulated by poultry manure and one of the sludges. In general, the two-fold greater rate of EOMs did not further accelerate the soil enzymes. The functional diversity of the soil microbiome was stimulated the most by cattle and goat manure. EOMs produce a shift in distribution of the most abundant bacterial phyla and additionally introduce exogenous bacterial genera to soil. Poultry and horse manure introduced the greatest number of new genera that were able to survive the strong competition in soil. EOMs differentiated plant growth in our study, which was correlated to the rate of nitrate release to soil. The detailed impacts of particular amendments were EOM-specific, but in general, no harm for microbial parameters was observed for manure and sludge application, regardless of their type. There was also no proof that the PAH and pesticide contents measured in manure or sludge had any effect on microbial activity and diversity.
Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jamshidi Parnian , Farsi Yeganeh , Nariman Zahra , Hatamnejad Mohammad Reza , Mohammadzadeh Benyamin , Akbarialiabad Hossein , Nasiri Mohammad Javad , Sechi Leonardo A.
Published: September 2023

Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients’ symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39–2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07–1.32), p = 0.11, and OR = 1.67, 95%CI (0.59–4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20–5.37), p = 0.01, and OR = 2.2, 95%CI (1.20–4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.
The Pulmonary Endothelial Glycocalyx Modifications in Glypican 1 Knockout Mice Do Not Affect Lung Endothelial Function in Physiological Conditions
Authors: Thota Lakshmi N. R. , Lopez Rosales Joaquin E. , Placencia Ivan , Zemskov Evgeny A. , Tonino Paola , Michael Ashley N. , Black Stephen M. , Chignalia Andreia Z.
Published: September 2023

The endothelial glycocalyx is a dynamic signaling surface layer that is involved in the maintenance of cellular homeostasis. The glycocalyx has a very diverse composition, with glycoproteins, proteoglycans, and glycosaminoglycans interacting with each other to form a mesh-like structure. Due to its highly interactive nature, little is known about the relative contribution of each glycocalyx constituent to its overall function. Investigating the individual roles of the glycocalyx components to cellular functions and system physiology is challenging, as the genetic manipulation of animals that target specific glycocalyx components may result in the development of a modified glycocalyx. Thus, it is crucial that genetically modified animal models for glycocalyx components are characterized and validated before the development of mechanistic studies. Among the glycocalyx components, glypican 1, which acts through eNOS-dependent mechanisms, has recently emerged as a player in cardiovascular diseases. Whether glypican 1 regulates eNOS in physiological conditions is unclear. Herein, we assessed how the deletion of glypican 1 affects the development of the pulmonary endothelial glycocalyx and the impact on eNOS activity and endothelial function. Male and female 5–9-week-old wild-type and glypican 1 knockout mice were used. Transmission electron microscopy, immunofluorescence, and immunoblotting assessed the glycocalyx structure and composition. eNOS activation and content were assessed by immunoblotting; nitric oxide production was assessed by the Griess reaction. The pulmonary phenotype was evaluated by histological signs of lung injury, in vivo measurement of lung mechanics, and pulmonary ventilation. Glypican 1 knockout mice showed a modified glycocalyx with increased glycocalyx thickness and heparan sulfate content and decreased expression of syndecan 4. These alterations were associated with decreased phosphorylation of eNOS at S1177. The production of nitric oxides was not affected by the deletion of glypican 1, and the endothelial barrier was preserved in glypican 1 knockout mice. Pulmonary compliance was decreased, and pulmonary ventilation was unaltered in glypican 1 knockout mice. Collectively, these data indicate that the deletion of glypican 1 may result in the modification of the glycocalyx without affecting basal lung endothelial function, validating this mouse model as a tool for mechanistic studies that investigate the role of glypican 1 in lung endothelial function.