bluuebunny/crossref_metadata_2025 huggingface dataset:
Multitarget adaptive virtual fixture based on task learning for hydraulic manipulator
Authors: Cheng Min , Li Renming , Ding Ruqi , Xu Bing
Published: July 2024

Heavy‐duty construction tasks implemented by hydraulic manipulators are highly challenging due to unstructured hazardous environments. Considering many tasks have quasirepetitive features (such as cyclic material handling or excavation), a multitarget adaptive virtual fixture (MAVF) method by teleoperation‐based learning from demonstration is proposed to improve task efficiency and safety, by generating an online variable assistance force on the master. First, the demonstration trajectory of picking scattered materials is learned to extract its distribution and the nominal trajectory is generated. Then, the MAVF is established and adjusted online by a defined nonlinear variable stiffness and position deviation from the nominal trajectory. An energy tank is introduced to regulate the stiffness so that passivity and stability can be ensured. Taking the operation mode without virtual fixture (VF) assistance and with traditional weighted adaptation VF as comparisons, two groups of tests with and without time delay were carried out to validate the proposed method.
Development and field evaluation of a VR/AR‐based remotely controlled system for a two‐wheel paddy transplanter
Authors: Lohan Shiv Kumar , Narang Mahesh Kumar , Raghuvirsinh Parmar , Kumar Santosh , Singh Lakhwinder Pal
Published: July 2024

Operating a two‐wheel paddy transplanter traditionally poses physical strain and cognitive workload challenges for farm workers, especially during headland turns. This study introduces a virtual reality (VR)/augmented reality (AR)based remote‐control system for a two‐wheel paddy transplanter to resolve these issues. The system replaces manual controls with VR interfaces, integrating gear motors and an electronic control unit. Front and rear‐view cameras provide real‐time field perception on light‐emitting diode screens, displaying path trajectories via an autopilot controller and real‐time kinematic global navigation satellite systems module. Human operators manipulate the machine using a hand‐held remote controller while observing live camera feeds and path navigation trajectories. The study found that forward speed necessitated optimization within manageable limits of 1.75–2.00 km h−1 for walk‐behind types and 2.00–2.25 km h−1 for remote‐controlled systems. While higher speeds enhanced field capacity by 11.67%–12.95%, they also resulted in 0.74%–1.17% lower field efficiency. Additionally, Operators' physiological workload analysis revealed significant differences between walk‐behind and remotely controlled operators. Significant differences in energy expenditure rate (EER) were observed between walk‐behind and remote‐controlled paddy transplanters, with EER values ranging from 8.20 ± 0.80 to 27.67 ± 0.45 kJ min⁻¹ and 7.56 ± 0.55 to 9.72 ± 0.37 kJ min⁻¹, respectively (p < 0.05). Overall, the VR‐based remote‐control system shows promise in enhancing operational efficiency and reducing physical strain in paddy transplanting operations.
Turning “green” into “gold”: A study on the impact of green finance pilot zone policy on energy carbon emission efficiency
Authors: Gao Jiazhan , Hua Guihong , Huo Baofeng
Published: July 2024

As a crucial mechanism for advancing sustainable development, green finance invigorates national initiatives to reach peak carbon emissions and achieve carbon neutrality. This study leverages panel data from 215 Chinese cities spanning 2013–2022, using the green finance pilot zone policy (GFZ) as a quasi‐natural experiment. By employing difference‐in‐differences methodologies, this research examines the effects of GFZ on energy carbon emission efficiency (ECE) in China, along with its spatial spillover impacts. The findings reveal a substantial enhancement in ECE attributable to GFZ, with results remaining robust through various stability checks. Mechanism analysis further indicates that GFZ boosts ECE by promoting green innovation and facilitating industrial upgrading and transformation. Additionally, heterogeneity analysis suggests that GFZ is more effective in cities with higher marketization levels. Improvements in ECE among different types of resource‐based cities are observed in the order of declining, regenerative, growing, and mature cities. Spatial analysis reveals that the spillover effects of GFZ peak at a distance of 500 km from the pilot zones. This study not only provides empirical evidence supporting the expansion of GFZ but also offers a unique Chinese perspective on sustainable development.
Trustworthy and collaborative traceability management: Experts’ feedback on a blockchain‐enabled framework
Authors: Demi Selina , Sánchez‐Gordón Mary , Kristiansen Monica , Larrucea Xabier
Published: July 2024

Blockchain technology has attracted significant attention in both academia and industry. Recently, the application of blockchain has been advocated in software engineering. The global software engineering paradigm exacerbates trust issues, as distributed and cross‐organizational teams need to share software artifacts. In such a context, there is a need for a decentralized yet reliable traceability knowledge base to keep track of what/how/when/by whom software artifacts were created or changed. This study presents a blockchain‐enabled framework for trustworthy and collaborative traceability management and identifies benefits, challenges, and potential improvements based on the feedback of software engineering experts. A qualitative approach was followed in this study through semistructured interviews with software engineering (SE) experts. Transcripts were analyzed by applying the content analysis technique. The results indicated the emergence of five categories, further grouped into three main categories: experts' perceptions, blockchain‐based software process improvement, and experts' recommendations. In addition, the findings suggested four archetypes of organizations that may be interested in blockchain technology: distributed organizations, organizations with contract‐based projects, organizations in regulated domains, and regulators who may push the use of this technology. Further efforts should be devoted to the integration of the proposal with tools used throughout the software development lifecycle and leveraging the potential of smart contracts in validating the implementation of requirements automatically.
Enhancing agricultural wireless sensor network security through integrated machine learning approaches
Authors: Sharma Ishu , Bhardwaj Aditya , Kaushik Keshav
Published: July 2024

Wireless sensor network (WSN) works with a collection of multiple sensor nodes to fetch the data from the deployed environment to fulfill the application whether it is agricultural monitoring, industrial monitoring, etc. The agricultural region can be monitored by deploying sensor nodes to multiple verticals where continuous human presence is not feasible. These devices are equipped with limited resources and are easily vulnerable to various cyber‐attacks. The attacker can hack the sensor nodes to steal critical information from WSN devices. The cluster heads in the WSN play a vital role in the process of routing data packets and attackers launch malicious codes through sender nodes to hack or damage the cluster heads to shut down the entire deployed network of agricultural regions. This research paper proposes a framework to improve the security of WSNs by providing a shield to the cluster heads of the network using machine learning techniques. The experimental study of the paper includes the comparative analysis of three machine learning techniques decision tree classifier, Gaussian Naïve Bayes, and random forest classifier for predicting WSN attacks like flooding, gray hole, blackhole, and TDMA that are deployed to support the proposed WSN security framework on the attack dataset. The random forest classifier achieves an accuracy of 98%, Precision of 97.6%, Recall of 97.6%, and F1 score of 97.8% which is the maximum among the deployed machine learning techniques.
A study on the sulfate erosion deterioration law and damage model of shotcrete in high geothermal tunnels
Authors: Tong Jianjun , Xiang Lulu , Cai Yanshan , Wang Mingnian , Ye Pei , Miao Xingwang
Published: July 2024

When building a tunnel in an environment rich in high‐temperature hot water, it is particularly necessary to pay attention to the influence of sulfate ions in underground hot water on tunnel shotcrete. In order to study the sulfate erosion mechanism and mechanical properties of shotcrete in a real high‐temperature hot water environment, this study was carried out by setting the curing temperature (20, 40, 60, and 80°C), humidity (55% RH, 95% RH), and erosion age (0, 15, 30, 60, and 90 d) as the test influencing factors; a full combination of dry‐wet cycle test was carried out, and the specimens under different conditions were analyzed macroscopically and microscopically. The results show that with the increase of the number of dry‐wet cycles, the quality of shotcrete increases first and then decreases, and the mechanical properties gradually decrease. In the early stage of erosion, the erosion product is mainly ettringite, and the macroscopic damage is aggregate spalling. In the later stage of erosion, the erosion product is mainly gypsum, and the macroscopic damage is expansion damage. Compared with standard curing, a certain degree of high temperature curing has little effect on the sulfate attack resistance of shotcrete, but when the curing temperature exceeds 60°C, the concrete is seriously damaged. Finally, by constructing the damage model of sulfate attack shotcrete, the variation of compressive strength of shotcrete with age after sulfate attack under different curing conditions was successfully predicted.
Strategies employed by EFL teachers to cope with language learners' classroom anxiety
Authors: Zarei Mohammad Amin , Alibakhshi Goudarz , Nezakatgoo Behzad
Published: July 2024

Language classroom anxiety is a significant concern for applied linguists and English language teachers. As an affective variable, foreign language anxiety has the potential to harm learners' language learning and performance. While the impact of language anxiety on the academic achievement of learners of English as a foreign language (EFL) has been extensively studied, little research has investigated the coping strategies of teachers to address learners' anxiety. This study aimed to explore such EFL teacher strategies in online English language classes, using a qualitative phenomenological research approach. The study involved in‐depth interviews with 20 teachers selected through theoretical sampling. The researchers used thematic analysis to analyze the interview data. The results revealed three factors that emerged from 24 identified coping strategies: creating a safe environment for EFL learners, utilizing learners' first language (L1), and engaging learners in classroom activities. These findings have theoretical and practical significance for teachers, educators, and administrators.
Pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid in rainbow trout (Oncorhynchus mykiss)
Authors: Corum Orhan , Durna Corum Duygu , Marin Pedro , Acar Omer Faruk , Aksoy Mert , Uney Kamil
Published: July 2024

Background

Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non‐steroidal anti‐inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties.

Objectives

The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C.

Methods

The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography–ultraviolet (UV) and pharmacokinetic parameters were assessed using non‐compartmental analysis.

Results

The elimination half‐life (t1/2ʎz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent.

Conclusions

While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
Taenia martis in an Alaotran gentle lemur (Hapalemur alaotrensis): The importance of molecular identification
Authors: Danière Clara , Callait‐Cardinal Marie‐Pierre , Grenouillet Frédéric , Lemberger Karin , Quintard Benoit
Published: July 2024

The cestode Taenia martis is a common parasite affecting mustelids, with rodents serving as intermediate hosts. However, infections with the larval stage have seldomly been described in primates. This report describes a case in an Alaotran gentle lemur (Hapalemur alaotrensis) that died of chronic kidney disease, and in which Taenia cysticercosis was discovered at postmortem examination. Microscopic examination of the cysts attached to the mesentery and the inner side of the ribs, combined with the epidemiology of Taenia cysticercosis in France, pointed to Taenia crassiceps as the most probable aetiology. However, molecular identification, undertaken 3 years later during a global study on T. crassiceps in lemurs in France, identified the larval cestode as T. martis. This report is the first record of T. martis infection in an Alaotran gentle lemur and shows the importance of molecular identification in cysticercosis diagnosis.
Hepatic T‐cell lymphoma in a dog with chronic hepatitis and presence of Leptospira spp. in hepatic tissue
Authors: Holenova Katerina , Giannasi Chiara , Alloway Elizabeth , Harper Aaron
Published: July 2024

A 7‐year‐old, female, neutered Border collie was referred for investigation of increased liver enzymes, accompanied by mild non‐specific clinical signs. Investigations subsequently revealed the presence of chronic pyogranulomatous hepatitis, copper accumulation and presence of multiplying Leptospira spp. in the liver tissue. Following treatment with doxycycline and D‐penicillamine, the liver parameters and clinical signs improved. However, 9 months after the treatment was initiated, the dog re‐presented for overall deterioration, small intestinal diarrhoea and cough. Investigations were consistent with a hepatic large cell lymphoma. The dog was euthanased shortly after diagnosis, and histopathology of the postmortem samples taken from the liver showed presence of CD3+, CD11d+ T‐cell lymphoma as well as multiplying Leptospira spp. in the tissue.
Water retention curves of sandy soils obtained from direct measurements, particle size distribution, and infiltration experiments
Authors: Farooq Umar , Gorczewska‐Langner Wioletta , Szymkiewicz Adam
Published: July 2024

Accurate information about soil water retention curves (SWRCs) of sands is essential for evaluating groundwater recharge and vulnerability to contamination in many shallow sandy aquifers which are widespread on post glacial areas in Northern Europe and North America. Pedotransfer functions (PTFs) allow to estimate SWRC from basic physical characteristics of soils, such as textural composition. However, in the case of clean sands which are dominated by a single textural fraction, PTFs should be based on more detailed information given by the particle size distribution. In this study we evaluated three parametric PTFs, which estimate parameters of the van Genuchten SWRC based on empirical correlations to the parameters of soil particle size distribution, and five semi‐physical PTFs, which derive the pore size distribution from particle size distribution. PTFs were compared to SWRCs fitted to the results of drainage experiments on sandy soil samples from six locations in Gdańsk region (northern Poland). Although in all samples the content of silt and clay fractions was low (<3.5%), the differences in actual content of fines strongly influenced the shape of SWRC. In contrast, the amount of gravel fraction (varying from 1% to 35%) did not have significant effect on SWRC. Semi‐physical PTFs were found to be more accurate than parametric PTFs. The best overall performance was shown by the semi‐physical Chang and Cheng PTF. Among the parametric PTFs the best accuracy was obtained with the Schaap and Bouten method. However, all considered functions showed limited accuracy in higher suction range. Additionally, infiltration experiments were performed on four sites. SWRCs were obtained from ring infiltrometer tests using the Beerkan estimation of soil transfer parameters (BEST) method and from the tension infiltrometer (TI) tests using numerical solution of the inverse problem based on the Richards equation. In almost all cases the wetting SWRCs were characterized by higher values of the pressure scaling parameter α compared to SWRCs measured in drainage experiments, which is consistent with the well‐known phenomenon of hysteresis in soils. However, the BEST method resulted in significantly higher α and hydraulic conductivity Ks than TI, probably due to activation of the largest soil pores during ponded infiltration.
Biodiversity offsetting destroys wildlife
Authors: Wilson Philip J.
Published: July 2024

Biodiversity offsetting is a net‐outcome policy by which metrics are used to quantify the loss of wildlife and habitat due to development (generally building for housing, industrial purposes or infrastructure). An equivalent or greater quantity of biodiversity is supposedly created, protected or restored elsewhere. The literature on the merit of biodiversity offsetting is equivocal, largely because the policy is prescriptive in favour of development but overlooks the conflict between development and environmental deterioration (much as in other policy within the ambit of ‘sustainable development'). The unadmitted contradiction can be seen relatively easily by appreciating that the site scale and wider scales are largely discrete. Even if biodiversity net gain really were achieved in going from site to site, the wider prejudice of development would still be the overriding influence in the observed (wide‐scale) decline of wildlife. By facilitating ever more human environmental impact, biodiversity offsetting does the opposite of what it purports to do; it destroys wildlife.
What Do Korean Speakers Know About Politeness?
Authors: Kim Soung-U. , Brown Lucien
Published: July 2024

This chapter explores how Korean speakers understand and talk about “politeness” and related metaconcepts. Data is drawn from qualitative interviews with 20 Korean speakers (10 students in their 20 s and 10 professors aged 40 and above). We asked them to provide their own personal definitions of six metaconcepts:yeyuy paluta‘possess correct civility’,yeyuy epsta‘lack civility’,concwunghata‘be respectful’,musihata‘be disrespectful’,chincelhata‘be courteous’, andpwulcincelhata‘be discourteous.’ We analyse how the participants defined these six concepts, and then look at four other important metalexemes that emerged in the data:phyenhata‘comfortable’,thayto‘embodied attitude’,paylye‘consideration’ andinceng‘recognition’. Through analysis of these different concepts, we are able to construct an emic (participant-oriented) picture of what politeness means across two different generations of Korean speakers. We conclude by discussing how the results compare to previous descriptions of politeness in Korean, and also to the models of politeness offered in previous politeness theories.
Exploring Frames and Negativity Strategies in the News During an Election Campaign
Authors: Kim Ji Young
Published: July 2024

This study aims to investigate news frames and the use of negativity in the mainstream news coverage during a presidential election campaign. From a strategic communication perspective, the messages’ cognitive and emotional (affective) attributes have been explored per time and political orientation of the media to discuss the implications on the campaign strategies.
Existence and convergence of the length-preserving elastic flow of clamped curves
Authors: Rupp Fabian , Spener Adrian
Published: July 2024

We study the evolution of curves with fixed length and clamped boundary conditions moving by the negative $$L^2$$

L
2

-gradient flow of the elastic energy. For any initial curve lying merely in the energy space we show existence and parabolic smoothing of the solution. Applying previous results on long-time existence and proving a constrained Łojasiewicz–Simon gradient inequality we furthermore show convergence to a critical point as time tends to infinity.
Tigliane metabolites in Hyles frass after feeding experiments with TPA and Euphorbia cyparissias
Authors: Kulossa Marie , Oertel Reinhard , Hundsdoerfer Anna K.
Published: July 2024

Within the genus Hyles, Euphorbia feeding appears to have evolved twice independently, in H. euphorbiae but also in H. nicaea, a species which had not been studied for its detoxification processes before. Euphorbia is known to contain toxic secondary metabolites, including diterpene esters, preventing most herbivores from feeding on them. We investigated the metabolisation of the standard phorbol ester Phorbol 12-myristate 13-acetate (TPA) and the diterpenes contained in Euphorbia cyparissias by the two species Hyles euphorbiae and Hyles nicaea (subspecies nicaea). For the first time, we report (1) The gut disposition of Hyles n. nicaea for this standard phorbol ester, which is commonly used in cancer and tumour research and (2) The disposition of the food plant tiglinaes of Euphorbia cyparissias after gut passage in both species and (3) Tigliane metabolites in the frass of TPA and of E. cyparissias feeding larvae. For both species around 5–25% of the TPA dose was recovered in the frass of the larvae, along with the metabolites phorbol and phorbol-13-acetate in very small amounts and traces. While the amounts of phorbol found did not differ much between the species frass, phorbol-13-acetate could be found in higher amounts in Hyles n. nicaea frass, indicating a difference in metabolisation. Moreover, enzymatic hydrolysis of TPA to phorbol-13-acetate and phorbol are postulated not to be the main metabolisation pathway, seeing that the amounts found only represent a small fraction of the TPA dose consumed.
Lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells is inhibited by microRNA-494-3p via targeting lipoprotein-associated phospholipase A2
Authors: Yan Wenxiao , Yan Yan , Luo Xinye , Dong Yansong , Liang Guiwen , Miao Hua , Huang Zhongwei , Jiang Haiyan
Published: July 2024

Background

Gram-negative bacterial lipopolysaccharide (LPS) is a major component of inflammation and plays a key role in the pathogenesis of sepsis. According to our previous study, the expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) is significantly upregulated in septic patients and is positively correlated with the severity of this disease. Herein, we investigated the potential roles of Lp-PLA2-targeting microRNAs (miRNAs) in LPS-induced inflammation in murine mononuclear macrophages (RAW264.7 cells).

Methods

In LPS-stimulated RAW264.7 cells, Lp-PLA2 was confirmed to be expressed during the inflammatory response. The function of microRNA-494-3p (miR-494-3p) in the LPS-induced inflammatory response of RAW264.7 cells was determined by the transfection of a miR-494-3p mimic or inhibitor in vitro.

Results

Compared to the control, LPS induced a significant increase in the Lp-PLA2 level, which was accompanied by the release of inflammatory mediators. The bioinformatics and qRT‒PCR results indicated that the miR-494-3p level was associated with Lp-PLA2 expression in the LPS-induced inflammatory response of RAW264.7 cells. Dual-luciferase reporter assay results confirmed that the 3’-UTR of Lp-PLA2 was a functional target of microRNA-494-3p. During the LPS-induced inflammatory response of RAW264.7 cells, targeting Lp-PLA2 and transfecting miR-494-3p mimics significantly upregulated the expression of miR-494-3p, leading to a reduction in the release of inflammatory factors and conferring a protective effect on LPS-stimulated RAW264.7 cells.

Conclusion

By targeting Lp-PLA2, miR-494-3p suppresses Lp-PLA2 secretion, thereby alleviating LPS-induced inflammation, which indicates that miR-494-3p may be a potential target for sepsis treatment.
Low-cost method to reduce interlayer voids in material extrusion: in situ layer-by-layer solvent treatment
Authors: Iqbal Muhammed Saqlain , Stano Gianni , Triminì Valentina , Percoco Gianluca
Published: July 2024

Material extrusion (MEX) is worldwide known as one of the most flexible additive manufacturing (AM) technologies for the fabrication of complex polymeric structures. However, the extremely high geometrical freedom has a price to pay: the presence of interlayer voids between consecutive extruded layers is the main backwards of MEX technology. Interlayer voids make 3D printed parts weaker (poor mechanical properties) compared to polymeric components fabricated by means of counterpart processes (i.e., injection molding). The present research work introduces a novel approach for the reduction of voids based on the layer-by-layer application of solvent vapor during the fabrication process, to smooth every single deposited layer. In this way, the new extruded layer has a greater area to bond with the previously extruded layer, resulting in an overall reduction of the porosity. The proposed approach is cost-effective, and it is based on the stop and go method enabled by MEX technologies: the fabrication process is paused after every layer, and when the solvent treatment is performed, the 3D printing process is resumed. The effectiveness of the layer-by-layer solvent vapor approach was evaluated, thereby resulting in a great reduction of the void density and average void area of 96%, and 79% respectively, and an increase of the wetting factor of 34%. Such findings pave the way for the exploitation of the proposed approach for the fabrication of complex structures with a reduced number of voids to be employed as structural components.
This must be the place: local amenities and superstars’ wages
Authors: Filomena Mattia , Principe Francesco
Published: July 2024

We investigate the role of local amenities in shaping compensating wage differentials in labor market populated by high-skilled workers. Using 10 years of longitudinal data on workers productivity along with information on firms and location amenities, we evaluate whether workers are willing to pay to join a better firm and if firms with undesirable attributes must provide higher wages to attract workers. By accounting for unobserved workers heterogeneity, we show that superstars receive positive wage differentials for lower location amenities as well as riskier employments.
Intellectual property rights protection and the dynamic gains from trade
Authors: Migueles Chazarreta Damián , Stepanok Ignat
Published: July 2024

This paper presents a dynamic general equilibrium model with two structurally identical open economies. Trade liberalization promotes innovation and growth when intellectual property rights (IPR) protection is sufficiently weak. Trade on the other hand does not affect innovation and growth when IPR protection is strong. We show that this result holds for both horizontal and vertical endogenous growth models, which have so far had contradictory predictions on how trade affects innovation. The reason for this supposed contradiction are implicit IPR protection assumptions in the two different types of growth models, strong protection in the horizontal model and weak protection in the vertical model. The IPR protection assumption makes a big difference for the size of the gains from trade. In a simple numerical example we show that assuming weak IPR protection can imply more than five times higher overall gains from trade. We also build a North–South model and add another aspect of IPR protection influencing the duration of Northern patents, namely imitation in the South. In the asymmetric model with a competitive fringe in the South, IPR protection no longer plays a crucial role for the dynamic gains from trade.
In vitro screening of understudied PFAS with a focus on lipid metabolism disruption
Authors: Kashobwe Lackson , Sadrabadi Faezeh , Braeuning Albert , Leonards Pim E. G. , Buhrke Thorsten , Hamers Timo
Published: July 2024

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals used in many industrial applications. Exposure to PFAS is associated with several health risks, including a decrease in infant birth weight, hepatoxicity, disruption of lipid metabolism, and decreased immune response. We used the in vitro cell models to screen six less studied PFAS [perfluorooctane sulfonamide (PFOSA), perfluoropentanoic acid (PFPeA), perfluoropropionic acid (PFPrA), 6:2 fluorotelomer alcohol (6:2 FTOH), 6:2 fluorotelomer sulfonic acid (6:2 FTSA), and 8:2 fluorotelomer sulfonic acid (8:2 FTSA)] for their capacity to activate nuclear receptors and to cause differential expression of genes involved in lipid metabolism. Cytotoxicity assays were run in parallel to exclude that observed differential gene expression was due to cytotoxicity. Based on the cytotoxicity assays and gene expression studies, PFOSA was shown to be more potent than other tested PFAS. PFOSA decreased the gene expression of crucial genes involved in bile acid synthesis and detoxification, cholesterol synthesis, bile acid and cholesterol transport, and lipid metabolism regulation. Except for 6:2 FTOH and 8:2 FTSA, all tested PFAS downregulated PPARA gene expression. The reporter gene assay also showed that 8:2 FTSA transactivated the farnesoid X receptor (FXR). Based on this study, PFOSA, 6:2 FTSA, and 8:2 FTSA were prioritized for further studies to confirm and understand their possible effects on hepatic lipid metabolism.
Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?
Authors: Doerr Adrian A. , Nordmeier Frederike , Walle Nadja , Laschke Matthias W. , Menger Michael D. , Meyer Markus R. , Schmidt Peter H. , Schaefer Nadine
Published: July 2024

Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC–MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.
The influence of travel time on perceived traveled distance varies by spatiotemporal scale
Authors: Jagorska Cindy , Riemer Martin
Published: July 2024

The influence of travel time on perceived traveled distance has often been studied, but the results are inconsistent regarding the relationship between the two magnitudes. We argue that this is due to differences in the lengths of investigated travel distances and hypothesize that the influence of travel time differs for rather short compared to rather long traveled distances. We tested this hypothesis in a virtual environment presented on a desktop as well as through a head-mounted display. Our results show that, for longer distances, more travel time leads to longer perceived distance, while we do not find an influence of travel time on shorter distances. The presentation through an HMD vs. desktop only influenced distance judgments in the short distance condition. These results are in line with the idea that the influence of travel time varies by the length of the traveled distance, and provide insights on the question of how distance perception in path integration studies is affected by travel time, thereby resolving inconsistencies reported in previous studies.
Sources and control of impurity during one-pot enzymatic production of dehydroepiandrosterone
Authors: Dai Jiawei , Wu Zheyi , Liu Zebin , Li Chen , Zhu Linjiang , Chen Hanchi , Chen Xiaolong
Published: July 2024

Dehydroepiandrosterone (DHEA) has a promising market due to its capacity to regulate human hormone levels as well as preventing and treating various diseases. We have established a chemical esterification coupled biocatalytic-based scheme by lipase-catalyzed 4-androstene-3,17-dione (4-AD) hydrolysis to obtain the intermediate product 5-androstene-3,17-dione (5-AD), which was then asymmetrically reduced by a ketoreductase from Sphingomonas wittichii (SwiKR). Co-enzyme required for KR is regenerated by a glucose dehydrogenase (GDH) from Bacillus subtilis. This scheme is more environmentally friendly and more efficient than the current DHEA synthesis pathway. However, a significant amount of 4-AD as by-product was detected during the catalytic process. Focused on the control of by-products, we investigated the source of 4-AD and identified that it is mainly derived from the isomerization activity of SwiKR and GDH. Increasing the proportion of glucose in the catalytic system as well as optimizing the catalytic conditions drastically reduced 4-AD from 24.7 to 6.5% of total substrate amount, and the final yield of DHEA achieved 40.1 g/L. Furthermore, this is the first time that both SwiKR and GDH have been proved to be promiscuous enzymes with dehydrogenase and ketosteroid isomerase (KSI) activities, expanding knowledge of the substrate diversity of the short-chain dehydrogenase family enzymes.

Key points

• A strategy of coupling lipase, ketoreductase, and glucose dehydrogenase in producing DHEA from 4-AD

• Both SwiKR and GDH are identified with ketosteroid isomerase activity.

• Development of catalytic strategy to control by-product and achieve highly selective DHEA production

Graphical abstract
Catabolism of 2-keto-3-deoxy-galactonate and the production of its enantiomers
Authors: Yun Eun Ju , Lee Sun-Hee , Kim Subin , Ryu Hae Seul , Kim Kyoung Heon
Published: July 2024

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal d-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for d-galactose catabolism. The presence of KDGal enantiomers, l-KDGal and d-KDGal, varies across these pathways. Fungal pathways generate l-KDGal through the reduction and dehydration of d-galacturonate, whereas bacterial pathways produce d-KDGal through the oxidation and dehydration of d-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that l-KDGal, identified in the bacterial catabolism of 3,6-anhydro-l-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and d- and l-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of l-KDGal and d-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers.

Key points

• KDGal is a metabolic intermediate in fungal and bacterial pathways

• Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal

• KDGal can be used to induce pectin catabolism or produce functional materials
Differences in the risk of immune-related pneumonitis between PD-1 and PD-L1 inhibitors: a meta-analysis according to the new mirror-principle and PRISMA guidelines
Authors: Tian Yuan , Yin Zongxiu , Zhang Chi , Li Zhuoqi , Wang Yuanyuan , Zhang Kai , Chen Feng , Dang Qi
Published: July 2024

Purpose

To compare the risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors, the meta-analysis was designed.

Method

The difference in risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors was assessed by two different meta-analysis methods, the Mirror-pairing and the PRISMA guidelines.

Results

A total of eighty-eight reports were used for meta-analysis, while thirty-two studies were used for the Mirror-pairing. Both PD-1 and PD-L1 inhibitors (used alone or combined with chemotherapy) increased the risk of developing immune-related pneumonitis (P < 0.00001; P < 0.00001). Based on indirect analyses results (subgroup analyses), the risk of PD-L1-induced pneumonitis was weaker than that of PD-1 inhibitors when the control group was chemotherapy (OR = 3.33 vs. 5.43) or placebo (OR = 2.53 vs. 3.19), while no obvious significant differences were found (P = 0.17; P = 0.53). For the Mirror-pairing-based meta-analysis, the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors (OR = 1.46, 95%CI [1.08, 1.98], I2 = 0%, Z = 2.47 (P = 0.01)). However, this difference was not significant, when they were combined with chemotherapy (OR = 1.05, 95%CI [0.68, 1.60], I2 = 38%, Z = 0.21 (P = 0.84)).

Conclusion

Both PD-1 and PD-L1 inhibitors increased the risk of immune-related pneumonitis, while the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors.
The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma
Authors: Xie Qingjian , Zeng Yuan , Zhang Xiangting , Yu Fujun
Published: July 2024

In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the oncogenic process. The microenvironment of hepatocellular carcinoma (HCC) is characterized by a pronounced infiltration of TAMs, underscoring their pivotal role in modulating the trajectory of the disease. Amidst the evolving therapeutic paradigms for HCC, the strategic reprogramming of metabolic pathways presents a promising avenue for intervention, garnering escalating interest within the scientific community. Previous investigations have predominantly focused on elucidating the mechanisms of metabolic reprogramming in cancer cells without paying sufficient attention to understanding how TAM metabolic reprogramming, particularly lipid metabolism, affects the progression of HCC. In this review article, we intend to elucidate how TAMs exert their regulatory effects via diverse pathways such as E2F1-E2F2-CPT2, LKB1-AMPK, and mTORC1-SREBP, and discuss correlations of TAMs with these processes and the characteristics of relevant pathways in HCC progression by consolidating various studies on TAM lipid uptake, storage, synthesis, and catabolism. It is our hope that our summary could delineate the impact of specific mechanisms underlying TAM lipid metabolic reprogramming on HCC progression and provide useful information for future research on HCC and the development of new treatment strategies.
TRP-2 / gp100 DNA vaccine and PD-1 checkpoint blockade combination for the treatment of intracranial tumors
Authors: Pearson Joshua R. D. , Puig-Saenz Carles , Thomas Jubini E. , Hardowar Lydia D. , Ahmad Murrium , Wainwright Louise C. , McVicar Adam M. , Brentville Victoria A. , Tinsley Chris J. , Pockley A. Graham , Durrant Lindy G. , McArdle Stephanie E. B.
Published: July 2024

Intracranial tumors present a significant therapeutic challenge due to their physiological location. Immunotherapy presents an attractive method for targeting these intracranial tumors due to relatively low toxicity and tumor specificity. Here we show that SCIB1, a TRP-2 and gp100 directed ImmunoBody® DNA vaccine, generates a strong TRP-2 specific immune response, as demonstrated by the high number of TRP2-specific IFNγ spots produced and the detection of a significant number of pentamer positive T cells in the spleen of vaccinated mice. Furthermore, vaccine-induced T cells were able to recognize and kill B16HHDII/DR1 cells after a short in vitro culture. Having found that glioblastoma multiforme (GBM) expresses significant levels of PD-L1 and IDO1, with PD-L1 correlating with poorer survival in patients with the mesenchymal subtype of GBM, we decided to combine SCIB1 ImmunoBody® with PD-1 immune checkpoint blockade to treat mice harboring intracranial tumors expressing TRP-2 and gp100. Time-to-death was significantly prolonged, and this correlated with increased CD4+ and CD8+ T cell infiltration in the tissue microenvironment (TME). However, in addition to PD-L1 and IDO, the GBM TME was found to contain a significant number of immunoregulatory T (Treg) cell-associated transcripts, and the presence of such cells is likely to significantly affect clinical outcome unless also tackled.
Safety and Performance of a Cell-Impermeable Endoprosthesis for Hemodialysis Vascular Access Outflow Stenosis: A Brazilian Multicenter Retrospective Study
Authors: Harduin Leonardo de Oliveira , Barroso Thiago Almeida , Guerra Julia Bandeira , Filippo Márcio Gomes , de Almeida Leonardo Cortizo , Vieira Brunno Ribeiro , Mello Renata Silveira , Galhardo Adriano Martins , Strogoff-de-Matos Jorge Paulo
Published: July 2024

Purpose

To evaluate the safety and performance of Wrapsody™, a cell-impermeable endoprosthesis (CIE), for treating hemodialysis vascular access outflow stenosis.

Materials and Methods

Investigators retrospectively analyzed 113 hemodialysis patients treated with a CIE (11/2021–12/2022) across four centers in Brazil. De novo or restenotic lesions were treated. The primary efficacy outcome measure was target lesion primary patency (TLPP) at 1, 3, 6, and 12 months; the primary safety outcome measure was the absence of serious local or systemic adverse events within the first 30 days post-procedure. Secondary outcome measures included technical and procedural success, access circuit primary patency (ACPP), and secondary patency at 1, 3, 6, and 12 months post-procedure.

Results

Thirty-nine patients (34.5%) had thrombosed access at the initial presentation, and 38 patients (33.6%) presented with recurrent stenosis. TLPP rates at 1, 3, 6, and 12 months were 100%, 96.4%, 86.4%, and 69.7%, respectively. ACPP rates were 100% at 1 month, 89.2% at 3 months, 70.9% at 6 months, and 56.0% at 12 months. The target lesion secondary patency rates at 1, 3, 6, and 12 months were 100%, 97.3%, 93.6%, and 91.7%, respectively. In the adjusted multivariate Cox regression analysis, male sex and endoprosthesis with diameters of 10, 12, 14, and 16 mm were associated with improved primary patency rates. No localized or systemic serious adverse event was observed through the first 30 days post-procedure.

Conclusion

The CIE evaluated in this study is safe and effective for treating peripheral and central outflow stenoses in hemodialysis vascular access.

Level of Evidence

Level 2b, cohort study.

Graphical Abstract
Symbiont community dynamics in the turbid reef specialist, Turbinaria reniformis, along a latitudinal and environmental gradient in Western Australia
Authors: Zweifler Adi , Evans Richard D. , Browne Nicola K. , Thomas Luke
Published: July 2024

Thermal stress triggers the breakdown of the obligate symbiosis between the cnidarian coral host and its autotrophic dinoflagellates of the family Symbiodiniaceae. This diverse family exhibits pronounced functional variation that has large implications for the survival of their coral host. In this study, we explored patterns of symbiont community composition and diversity in the coral Turbinaria reniformis, a turbid reef specialist, along a latitudinal and environmental gradient in Western Australia. Using metabarcoding of the internal transcribed spacer region 2, we explored symbiont community patterns, their environmental drivers, and potential associations with host genetic structure. Our findings reveal a predominance of Cladocopium across our study area, with distinct regional composition influenced primarily by sea surface temperature. Geographical distance and host genetic data did not align with symbiont community divergence, suggesting a complex interplay of environmental and genetic factors t shaping the community structure. This study underscores Cladocopium stability in Western Australia across large distances and strong environmental gradients. It also highlights the highly diversified lineage community that may explain T. reniformis ability to thrive in a wide range of environmental conditions.
Die aktuelle IC3D-Klassifikation der Hornhautdystrophien – Übersicht und Änderungen der 3. Auflage
Authors: Berger Tim , Weiss Jayne S. , Lisch Walter , Seitz Berthold
Published: July 2024

Das Internationale Komitee für die Klassifikation von Hornhautdystrophien („International Committee on Classification of Corneal Dystrophies“ [IC3D]) wurde im Jahr 2005 gegründet, um Schwierigkeiten zu beseitigen, die sich aus der veralteten Nomenklatur für Hornhautdystrophien (HD) ergaben, und um Fehleinschätzungen in der Literatur zu korrigieren. Für jede der 22 HD wurde eine eigene Vorlage (sog. „Template“) erstellt, die den aktuellen klinischen, pathologischen und genetischen Wissensstand über die Erkrankung widerspiegelt. Darüber hinaus enthält jedes „Template“ repräsentative klinische Fotografien sowie licht- und elektronenmikroskopische Bilder und, falls vorhanden, konfokalmikroskopische und kohärenztomographische Aufnahmen der jeweiligen HD. Nach Veröffentlichung der ersten Ausgabe im Jahr 2008 folgte 2015 die überarbeitete Version. Die dritte Ausgabe der IC3D wurde im Februar 2024 veröffentlicht und ist frei zugänglich. Die neueste Auflage soll als Nachschlagewerk im klinischen Alltag dienen und die Diagnose von HD erleichtern. Dieser Artikel bietet einen Überblick über die Diagnose- und Behandlungsprinzipien der HD und stellt die IC3D und deren Veränderungen im Laufe der Zeit vor.