bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Metaldehyde on Survival, Enzyme Activities, and Histopathology of the Apple Snail Pomacea canaliculata (Lamarck 1822)
Authors: Liu Jimin , Chen Xuan , Zhang Jiaen , Yao Fucheng , Shi Zhaoji , Chen Yingtong , Chen Qi , Qin Zhong
Published: June 2024

Pomacea canaliculata, as an invasive exotic species in Asia, can adversely affect crop yields, eco-environment, and human health. Application of molluscicides containing metaldehyde is one effective method for controlling P. canaliculata. In order to investigate the effects of metaldehyde on adult snails, we conducted acute toxicological experiments to investigate the changes in enzyme activities and histopathology after 24 h and 48 h of metaldehyde action. The results showed that the median lethal concentrations (LC) of metaldehyde on P. canaliculata were 3.792, 2.195, 1.833, and 1.706 mg/L at exposure times of 24, 48, 72, and 96 h, respectively. Treatment and time significantly affected acetylcholinesterase (AChE), glutathione S-transferase (GST), and total antioxidant capacity (TAC) activity, with sex significantly affecting AChE, GST, and TAC activity and time significantly affecting carboxylesterase (CarE). In addition, the interaction of treatment and time significantly affected the activity of GST, CarE and TAC. In addition, histopathological changes occurred in the digestive glands, gills and gastropods of apple snail exposed to metaldehyde. Histological examination of the digestive glands included atrophy of the digestive cells, widening of the hemolymph gap, and an increase in basophils. In treated snails, the hemolymph gap in the gills was widely dilated, the columnar cells were disorganized or even necrotic, and the columnar muscle cells in the ventral foot were loosely arranged and the muscle fibers reduced. The findings of this study can provide some references for controlling the toxicity mechanism of invasive species.
Genetic Analysis and Fine Mapping of QTL for the Erect Leaf in Mutant mths29 Induced through Fast Neutron in Wheat
Authors: Yang Zhixin , Gu Jiayu , Zhao Minghui , Fan Xiaofeng , Guo Huijun , Xie Yongdun , Zhang Jinfeng , Xiong Hongchun , Zhao Linshu , Zhao Shirong , Ding Yuping , Kong Fuquan , Sui Li , Xu Le , Liu Luxiang
Published: June 2024

The erect leaf plays a crucial role in determining plant architecture, with its growth and development regulated by genetic factors. However, there has been a lack of comprehensive studies on the regulatory mechanisms governing wheat lamina joint development, thus failing to meet current breeding demands. In this study, a wheat erect leaf mutant, mths29, induced via fast neutron mutagenesis, was utilized for QTL fine mapping and investigation of lamina joint development. Genetic analysis of segregating populations derived from mths29 and Jimai22 revealed that the erect leaf trait was controlled by a dominant single gene. Using BSR sequencing and map-based cloning techniques, the QTL responsible for the erect leaf trait was mapped to a 1.03 Mb physical region on chromosome 5A. Transcriptome analysis highlighted differential expression of genes associated with cell division and proliferation, as well as several crucial transcription factors and kinases implicated in lamina joint development, particularly in the boundary cells of the preligule zone in mths29. These findings establish a solid foundation for understanding lamina joint development and hold promise for potential improvements in wheat plant architecture.
Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage
Authors: Thangameeran Shaik Ismail Mohammed , Tsai Sheng-Tzung , Liew Hock-Kean , Pang Cheng-Yoong
Published: June 2024

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
New Heterostilbene and Triazole Oximes as Potential CNS-Active and Cholinesterase-Targeted Therapeutics
Authors: Mlakić Milena , Čadež Tena , Šinko Goran , Škorić Irena , Kovarik Zrinka
Published: June 2024

New furan, thiophene, and triazole oximes were synthesized through several-step reaction paths to investigate their potential for the development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Treating patients with acute OP poisoning is still a challenge despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, is blocked by OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to a cholinergic crisis. The oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper, we described the synthesis of 63 heterostilbene derivatives, of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents–sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in the micromolar range, we identified several oximes as BChE or AChE selective inhibitors with the potential for drug development. Furthermore, the oximes were poor reactivators of AChE; four heterocyclic derivatives reactivated cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had a reactivation efficacy comparable to the standard oxime HI-6. In silico analysis and molecular docking studies, including molecular dynamics simulation, connected kinetic data to the structural features of these oximes and confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer
Authors: Sekihara Kazumasa , Himuro Hidetomo , Toda Soji , Saito Nao , Hirayama Ryoichi , Suganuma Nobuyasu , Sasada Tetsuro , Hoshino Daisuke
Published: June 2024

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy characterized by advanced disease at diagnosis and a poor prognosis. Despite multimodal therapeutic approaches that include surgery, radiotherapy, and chemotherapy, an optimal treatment strategy remains elusive. Current developments in targeted therapies and immunotherapy offer promising avenues for improved outcomes, particularly for BRAF-mutant patients. However, challenges remain regarding overcoming drug resistance and developing effective treatments for BRAF-wild-type tumors. This comprehensive review examines the clinical and biological features of ATC, outlines the current standards of care, and discusses recent developments with a focus on the evolving role of radiotherapy. Moreover, it emphasizes the necessity of a multidisciplinary approach and highlights the urgent need for further research to better understand ATC pathogenesis and identify new therapeutic targets. Collaborative efforts, including large-scale clinical trials, are essential for translating these findings into improved patient outcomes.
Do Dark Humour Users Have Dark Tendencies? Relationships between Dark Humour, the Dark Tetrad, and Online Trolling
Authors: Voisey Sophie , Heintz Sonja
Published: June 2024

Humour and antisocial behaviour on the internet are under-researched. Online spaces have opened a gateway for new ways to express unrestrained humour (e.g., dark humour) and ways to behave antisocially (e.g., online trolling). The tendencies and motivations of those engaging with such humour and behaviour are yet to be clearly established and understood. The present study aimed to fill this gap by exploring the interplay between dark humour, online trolling, and dark personality traits. Participants (N = 160) completed an online survey consisting of trait scales to assess the Dark Tetrad, dark humour, and online trolling, as well as two online trolling tasks (enjoyment and ability) and two dark humour meme tasks (enjoyment and ability). The results confirmed relationships between the Dark Tetrad and the dark humour trait, and several Dark Tetrad traits were related to the enjoyment of and ability to produce dark humour. Furthermore, dark humour and online trolling were closely related. The findings also revealed that online trolls did not enjoy being trolled but did enjoy trolling, and this ability to troll is underpinned by sadism. These findings illustrate the potential dark psychological motivations for using dark humour, demonstrate that online trolling is infused with darker forms of humour, and provide deeper insights into online trolls.
Building Energy Efficiency Enhancement through Thermochromic Powder-Based Temperature-Adaptive Radiative Cooling Roofs
Authors: Song Ge , Zhang Kai , Xiao Fei , Zhang Zihao , Jiao Siying , Gong Yanfeng
Published: June 2024

This paper proposes a temperature-adaptive radiative cooling (TARC) coating with simple preparation, cost effectiveness, and large-scale application based on a thermochromic powder. To determine the energy efficiency of the proposed TARC coating, the heat transfer on the surface of the TARC coating was analyzed. Then, a typical two-story residential building with a roof area of 258.43 m2 was modeled using EnergyPlus. Finally, the energy-saving potential and carbon emission reduction resulting from the application of the proposed TARC roof in buildings under different climates in China were discussed. The results showed that the average solar reflectivity under visible light wavelengths (0.38–0.78 μm) decreases from 0.71 to 0.37 when the TARC coating changes from cooling mode to heating mode. Furthermore, energy consumption can be reduced by approximately 17.8–43.0 MJ/m2 and 2.0–32.6 MJ/m2 for buildings with TARC roofs compared to those with asphalt shingle roofs and passive daytime radiative cooling (PDRC) roofs, respectively. This also leads to reductions in carbon emissions of 9.4–38.0 kgCO2/m2 and 1.0–28.9 kgCO2/m2 for the buildings located in the selected cities. To enhance building energy efficiency, TARC roofs and PDRC roofs are more suitable for use on buildings located in zones with high heating demands and high cooling demands, respectively.
Energy Performance of a University Building for Different Air Conditioning (AC) Technologies: A Case Study
Authors: Balbis-Morejón Milen , Cabello-Eras Juan José , Rey-Martínez Francisco J. , Fandiño Jorge Mario Mendoza , Rey-Hernández Javier M.
Published: June 2024

The study uses four AC technologies to assess the energy performance—this is a case study of an educational building in Barranquilla, Colombia. The building currently has split AC technology high-energy consumers. Therefore, it was necessary to assess a replacement with more efficient technology. Because of the non-seasonal climate in the building location, one month of monitoring of energy consumption was the reference for developing an energy model for the building using EnergyPlus and DesignBuilder software. The model was applied to forecast the building energy performance of our more efficient AC technologies available in the Colombian market, and valuable according to building specifications (Split, VRF, VAV, and Chiller). Results show a reduction in energy consumption of approximately 30% with the technology change and 15% savings in life cycle costs (LCCs), even though the building is already considered to have a low energy consumption according to national regulations. The findings of this study underscore the potential for widespread applicability across all types of buildings, regardless of their energy consumption profile, be it low, medium, or high. This extensive applicability not only highlights the adaptability and versatility of the technology but also underscores its significance in achieving substantial energy savings and cost reductions across the entire building industry, contributing to a more sustainable and economically efficient future.
Optimization of Composition of Waterproofing Material Based on Modified Fine-Grained Concrete
Authors: Zhukov Aleksey , Bazhenova Sofia , Stepina Irina , Erofeeva Irina
Published: June 2024

The purpose of the research described in this article was to optimize the compositions based on hydraulic-modified binder and construction waste for waterproofing and repair of concrete or brick structures in contact with the ground, as well as the study of properties and development of the basis of the methodology for selecting the composition of such a waterproofing system. Processing of the results of the experiment was carried out by statistical and analytical methods. The research was based on a method for determining the adhesive strength of a waterproofing coating, based on the determination when the insulating layers are torn off. As a result of the calculation and experimental verification, the composition of the waterproofing material was obtained, which corresponds to an adhesive strength of 3.8 MPa; the strength of the waterproofing layer was 36–37 MPa, as well as the amounts of the main components: acrylic resin 3.9%; finely ground concrete waste 80 kg/m3; plasticizer consumption (0.38…0.39%) at the optimum moisture content of the base surface (9.7…9.8%).
Correction: Ghansah, F.A.; Edwards, D.J. Digital Technologies for Quality Assurance in the Construction Industry: Current Trend and Future Research Directions towards Industry 4.0. Buildings 2024, 14, 844
Authors: Ghansah Frank Ato , Edwards David John
Published: June 2024

In the publication [...]
Fostering Social Sustainability: Inclusive Communities through Prefabricated Housing
Authors: Ziaesaeidi Parisa , Noroozinejad Farsangi Ehsan
Published: June 2024

Over the last decade, many major cities have experienced a housing crisis to keep pace with patterns of urban population growth. Housing continues to face many challenges such as land use, regulatory issues, and environmental issues. In recent years, new housing research has also revealed that prefabricated housing could indirectly be a solution to environmental issues, as the housing sector has observed an increase in demand for eco-friendly housing solutions. However, while prefabricated housing can be a solution to issues of environmental concerns, it still needs more research to explore its influence on social sustainability. Therefore, this opinion paper investigates how socially sustainable communities could be feasible and practicable through prefabricated housing. In this opinion paper, the social sustainability principles in relation to prefabricated housing was analysed to show situations that can be complex with the benefits and challenges as well. The main objective of this study was to find the potential of prefabricated housing to promote social sustainability, with proper analysis of this housing influence on the key elements of community, diversity as well as adaptability. A survey based on the aspect of social sustainability of prefabricated housing was conducted to collect various perspectives that may influence the future trend in the housing sector, hence making necessary steps towards socially sustainable prefabricated housing solutions. The survey findings highlight the social element of prefabricated households, which refers to how accessible as well as adaptable the prefabricated homes are in terms of targets, build and social group, encouraging dwellers’ interaction and participation, which facilitates the implementation of a sense of belonging and social cohesion among societies.
A 3D Parameterized BIM-Modeling Method for Complex Engineering Structures in Building Construction Projects
Authors: Yang Lijun , Gao Xuexiang , Chen Song , Li Qianyao , Bai Shuo
Published: June 2024

The structural components of large-scale public construction projects are more complex than those of ordinary residential buildings, with irregular and diverse components, as well as a large number of repetitive structural elements, which increase the difficulty of BIM-modeling operations. Additionally, there is a significant amount of inherent parameter information in the construction process, which puts forward higher requirements for the application and management capabilities of BIM technology. However, the current BIM software still has deficiencies in the parameterization of complex and irregular structural components, fine modeling, and project management information. To address these issues, this paper takes Grasshopper as the core parametric tool and Revit as the carrier of component attribute information. It investigates the parametric modeling logic of Grasshopper and combines the concepts of parameterization, modularization, standardization, and engineering practicality to create a series of parametric programs for complex structural components in building projects. This approach mainly addresses intricate challenges pertaining to the parametric structural shapes (including batch processing) and parametric structural attributes (including the batch processing of diverse attribute parameters), thereby ensuring the efficiency in BIM modeling throughout the design and construction phases of complex building projects.
A Study on Spatiotemporal Dynamics and Spatial Dependence of Sound Source Perception in Fuzhou Historical and Cultural Districts
Authors: Wu Lin , Zhang Qiqi , Yan Yulan , Lan Ting , Hu Yanfang , Zhang Yijing , He Tianyou , Ye Jing
Published: June 2024

As a carrier of cultural characteristics of historic districts, the soundscape has unique advantages in shaping regional cultural personality, and mastering its spatiotemporal characteristics is crucial for preserving soundscape heritage with natural and humanistic environments as its kernel. Focusing on the Three Square and Seven Alleys historic and cultural district in Fuzhou, this paper analyzes the spatial and temporal patterns of the physical acoustic indicators of the soundscape, the spatial dependence of the sound source harmony, and the spatial relationship between the two. It was found that the physical acoustic indicators showed dynamic changes in spatial and temporal scales and reflect specific human activity and behavioral patterns; sound source harmony showed spatial autocorrelation in both global and local models, with prominent spatial characteristics; and the physical acoustic indicators may negatively affect soundscape perception. The study emphasizes the importance of the regional cultural connotation of soundscape in urban planning. It provides a scientific basis for the planning, designing, and managing of soundscape resources in historic and cultural districts and world heritage sites.
Analysis and Real-Time Monitoring of the Influence of Wind Load on a High-Altitude Steel Connecting Bridge with Small Spacing
Authors: Wu Xinye , Chen Shenghui , Hu Yixin , Wang Zhiwei , Li Zhengke
Published: June 2024

With the development of steel-structure construction technology in high-rise buildings, the design and construction of high-rise steel structures tend to be complicated. Based on the Zhuhai Tiejian Square project, the fluid-structure coupling calculation analysis and on-site monitoring are carried out in view of the wind load of the high-altitude steel-structure connecting bridge in the hoisting stage of the Zhuhai Tiejian Square project. The main structure of the project is four towers and five high-altitude, small-spacing steel structures connecting the four towers. The lifting process of the third zone is taken as the analysis object, and the hoisting idea of “low-altitude hoisting, overall lifting” is adopted. Because the span of the high-altitude steel-structure connecting bridge is small and the installation height is high, the influence of wind load on the hoisting process cannot be ignored. Therefore, the unidirectional fluid-structure coupling model of the high-altitude small-space steel-structure connecting bridge in the third zone was established by using CFD calculation software ANSYS Fluent 2022 R1, and the corresponding flow field and solid calculation results were obtained and analyzed. The analysis results show that the lifting structure still produces a certain deformation when the wind speed is 5 m/s or 10 m/s, and the calculation results show that the stress calculation results are still within the safe range of steel strength for the sensitivity of the lifting structure under wind load. With the increase of wind speed, the local maximum stress of the structure increases greatly, but the overall deformation remains stable, which indicates that the greatest challenge of hoisting steel structures under wind load may be the stability direction rather than the strength, so it is necessary to strictly monitor the displacement deformation of the structure during construction. Then, through the monitoring of the overall lifting process of the high-altitude, large-span, steel-connected structure of Zhuhai Tiejian Square from pre-lifting to formal lifting, real-time monitoring and data analysis show that the lifting process of the high-altitude steel bridge of Zhuhai Tiejian Square is safe and reliable, the force transformation of each component is reasonable, the lifting process is relatively stable, the external environment has little impact, and the expected monitoring effect has been achieved. The calculation simulation and on-site monitoring in this paper can provide theoretical and practical guidance for the construction safety under the influence of wind load in the construction process of high-altitude steel-structure hoisting, and provide an important reference value for similar projects.
Research on Rock-Breaking Characteristics of Cutters and Matching of Cutter Spacing and Penetration for Tunnel Boring Machine
Authors: Zhang Huipeng , Xia Ming , Huang Fengyuan , Zhang Zhiqiang
Published: June 2024

Tunnel boring machine (TBM) tunnel construction in composite strata relies heavily on understanding the rock-breaking characteristics of TBM cutters and optimizing cutter spacing and penetration. Utilizing a full-scale rock rotary cutting machine (RCM), this study conducted rock-breaking tests with disc cutters under varying rolling radii. An analysis of rock debris shape and cutter behavior provided insights into rock-breaking mechanisms. Two main types of rock fragments were identified, with both shear and compression failure observed during cutter–rock interactions. The influence of the rolling radius and cutter spacing on cutter forces was analyzed, along with numerical modeling using the particle flow method. Optimal cutter selection in soft–hard composite strata should prioritize cutter force, with the greatest force required in hard rock. Cutter force increases with penetration, while the force difference between cutters decreases with reduced cutter spacing. These findings offer practical guidance for efficient rock-breaking in composite geological formations during tunnel construction.
Exploring the Impact of Facade Color Elements on Visual Comfort in Old Residential Buildings in Shanghai: Insights from Eye-Tracking Technology
Authors: Wang Zhanzhu , Shen Maoting , Huang Yongming
Published: June 2024

Building façade color plays a key role in shaping urban image, enhancing urban vitality, and optimizing citizens’ living experience. Moreover, colors can influence people’s perception of space, but the multiple interrelationships between color elements and users’ color evaluation and visual perception have not yet been thoroughly studied. In order to explore the relationships between color elements and visual perception and subjective comfort, this study discusses the matching relationship between color and the comfort of a residential building façade from three levels of color hue, lightness, and saturation by combining eye movement technology and a subjective evaluation. Taking Anshan San Village in Shanghai as the research object, the relationship model between color elements, visual perception, and subjective comfort is established through correlation analysis, linear regression, and multifactor regression analysis, and the correlation between single elements and multiple elements is explored from multi-dimensional perspectives. It aims to assess the operability of eye movement data as a measure of the visual comfort with the residential building façade color through multiple indicators and to explore and establish a new correlation assessment framework between the three attributes of façade color and users’ visual comfort. The results show that (1) highly saturated façade colors significantly increase cognitive load and decrease color evaluation. (2) Brightness has a non-linear relationship with visual perception and subjective evaluation, either too high or too low a brightness value will cause visual fatigue and thus reduce the color evaluation, and when the brightness is maintained at 40–80%, there will be a better color experience. (3) Warm tones such as red, orange, and yellow can strengthen the color perception to enhance the color evaluation of the façade; among cold tones, cyan and purple can also strengthen the visual perception of the color of the façade to enhance the color evaluation. After validation, the proposed new color comfort assessment method is feasible and comprehensive, and we hope it can provide a reference for the planning of old residential buildings and communities in the future.
Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma
Authors: Sanai Faisal M. , Odah Hassan O. , Alshammari Kanan , Alzanbagi Adnan , Alsubhi Murooj , Tamim Hani , Alolayan Ashwaq , Alshehri Ahmed , Alqahtani Saleh A.
Published: June 2024

Background: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. Methods: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. Results: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9–49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6–18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1–3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2–6.3). Conclusion: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.
Recent Advances of PtCu Alloy in Electrocatalysis: Innovations and Applications
Authors: Shen Ziyang , Tang Jinyao , Shen Xiaochen
Published: June 2024

Developing highly active and durable platinum-based catalysts is crucial for electrochemical renewable energy conversion technologies but the limited supply and high cost of platinum have hindered their widespread implementation. The incorporation of non-noble metals, particularly copper, into Pt catalysts has been demonstrated as an effective solution to reduce Pt consumption while further promoting their performance, making them promising for various electrocatalytic reactions. This review summarizes the latest advances in PtCu-based alloy catalysts over the past several years from both synthetic and applied perspectives. In the synthesis section, the selection of support and reagents, synthesis routes, as well as post-treatment methods at high temperatures are reviewed. The application section focuses not only on newly proposed electrochemical reactions such as nitrogen-related reactions and O2 reduction but also extends to device-level applications. The discussion in this review aims to provide further insights and guidance for the development of PtCu electrocatalysts for practical applications.
Transcription Factor-Mediated Generation of Dopaminergic Neurons from Human iPSCs—A Comparison of Methods
Authors: McDonald Kirstin O. , Lyons Nikita M. A. , Gray Luca K. C. , Xu Janet B. , Schoderboeck Lucia , Hughes Stephanie M. , Basak Indranil
Published: June 2024

Dopaminergic neurons are the predominant brain cells affected in Parkinson’s disease. With the limited availability of live human brain dopaminergic neurons to study pathological mechanisms of Parkinson’s disease, dopaminergic neurons have been generated from human-skin-cell-derived induced pluripotent stem cells. Originally, induced pluripotent stem-cell-derived dopaminergic neurons were generated using small molecules. These neurons took more than two months to mature. However, the transcription-factor-mediated differentiation of induced pluripotent stem cells has revealed quicker and cheaper methods to generate dopaminergic neurons. In this study, we compared and contrasted three protocols to generate induced pluripotent stem-cell-derived dopaminergic neurons using transcription-factor-mediated directed differentiation. We deviated from the established protocols using lentivirus transduction to stably integrate different transcription factors into the AAVS1 safe harbour locus of induced pluripotent stem cells. We used different media compositions to generate more than 90% of neurons in the culture, out of which more than 85% of the neurons were dopaminergic neurons within three weeks. Therefore, from our comparative study, we reveal that a combination of transcription factors along with small molecule treatment may be required to generate a pure population of human dopaminergic neurons.
Biallelic Variants in MNS1 Are Associated with Laterality Defects and Respiratory Involvement
Authors: Hjeij Rim , Leslie Joseph , Rizk Hoda , Dworniczak Bernd , Olbrich Heike , Raidt Johanna , Bode Sebastian Felix Nepomuk , Gardham Alice , Stals Karen , Al-Haggar Mohammad , Osman Engy , Crosby Andrew , Eldesoky Tarek , Baple Emma , Omran Heymut
Published: June 2024

Defects in motile cilia, termed motile ciliopathies, result in clinical manifestations affecting the respiratory and reproductive system, as well as laterality defects and hydrocephalus. We previously defined biallelic MNS1 variants causing situs inversus and male infertility, mirroring the findings in Mns1−/− mice. Here, we present clinical and genomic findings in five newly identified individuals from four unrelated families affected by MNS1-related disorder. Ciliopathy panel testing and whole exome sequencing identified one previously reported and two novel MNS1 variants extending the genotypic spectrum of disease. A broad spectrum of laterality defects including situs inversus totalis and heterotaxia was confirmed. Interestingly, a single affected six-year-old girl homozygous for an MNS1 nonsense variant presented with a history of neonatal respiratory distress syndrome, recurrent respiratory tract infections, chronic rhinitis, and wet cough. Accordingly, immunofluorescence analysis showed the absence of MNS1 from the respiratory epithelial cells of this individual. Two other individuals with hypomorphic variants showed laterality defects and mild respiratory phenotype. This study represents the first observation of heterotaxia and respiratory disease in individuals with biallelic MNS1 variants, an important extension of the phenotype associated with MNS1-related motile ciliopathy disorder.
Mycobacterium tuberculosis FadD18 Promotes Proinflammatory Cytokine Secretion to Inhibit the Intracellular Survival of Bacillus Calmette–Guérin
Authors: Peng Yongchong , Tang Tian , Li Qianqian , Zhou Shiying , Sun Qin , Zhou Xinjun , Zhu Yifan , Wang Chao , Bermudez Luiz E. , Liu Han , Chen Huanchun , Guo Aizhen , Chen Yingyu
Published: June 2024

Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette–Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines.
Digital Pathology Identifies Associations between Tissue Inflammatory Biomarkers and Multiple Sclerosis Outcomes
Authors: Cooze Benjamin , Neal James , Vineed Alka , Oliveira J. C. , Griffiths Lauren , Allen K. H. , Hawkins Kristen , Yadanar Htoo , Gerhards Krisjanis , Farkas Ildiko , Reynolds Richard , Howell Owain
Published: June 2024

Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Methods: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38–98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Results: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Conclusion: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.
Innovating in an Uncertain World: Understanding the Social, Technical and Systemic Barriers to Farmers Adopting New Technologies
Authors: Manning Louise
Published: June 2024

The current geopolitical and socioeconomic landscape creates a difficult and uncertain operating environment for farming and agri-food businesses. Technological innovation has not been suggested to be a “silver bullet” but is one of the ways organizations can seek to reduce environmental impact, deliver net zero, address the rural skills and labor deficit and produce more output from fewer resources and as a result, make space for nature. But what barriers limit this promissory narrative from delivering in practice? The purpose of the paper is to firstly explore the reported social, technical and systemic barriers to agri-technology adoption in an increasingly uncertain world and then secondly identify potential research gaps that highlight areas for future research and inform key research questions. Socio-technical and infrastructural barriers have been identified within the context of the complex hollowing out and infilling of rural communities across the world. These barriers include seventeen factors that emerge, firstly those external to the farm (economic conditions, external conditions including bureaucracy, market conditions, weather uncertainty and the narratives about farmers), those internal to the farm business (farming conditions, employee relations, general finance, technology and time pressures) and then personal factors (living conditions, personal finances, physical health, role conflict, social isolation and social pressure). Adaptive resilience strategies at personal, organizational and community levels are essential to address these barriers and to navigate agri-technology adoption in an uncertain and dynamic world.
Drug-Resistance Biomarkers in Patient-Derived Colorectal Cancer Organoid and Fibroblast Co-Culture System
Authors: Ryu Kyoung-Bin , Seo Jeong-ah , Lee Kyerim , Choi Juhyun , Yoo Geon , Ha Ji-hye , Ahn Mee Ryung
Published: June 2024

Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. We used an indirect co-culture system comprising colorectal cancer organoids and cancer-associated fibroblasts to simulate the tumor microenvironment. Immunofluorescence staining validated the characteristics of both organoids and fibroblasts, showing high expression of epithelial cell markers (EPCAM), colon cancer markers (CK20), proliferation markers (KI67), and fibroblast markers (VIM, SMA). Transcriptome profiling was conducted after treatment with anticancer drugs, such as 5-fluorouracil and oxaliplatin, to identify chemoresistance-related genes. Changes in gene expression in the co-cultured colorectal cancer organoids following anticancer drug treatment, compared to monocultured organoids, particularly in pathways related to interferon-alpha/beta signaling and major histocompatibility complex class II protein complex assembly, were identified. These two gene groups potentially mediate drug resistance associated with JAK/STAT signaling. The interaction between colorectal cancer organoids and fibroblasts crucially modulates the expression of genes related to drug resistance. These findings suggest that the interaction between colorectal cancer organoids and fibroblasts significantly influences gene expression related to drug resistance, highlighting potential biomarkers and therapeutic targets for overcoming chemoresistance. Enhanced understanding of the interactions between cancer cells and their microenvironment can lead to advancements in personalized medical research..
An Investigation of the Effect of pH on Micelle Formation by a Glutamic Acid-Based Biosurfactant
Authors: Mayer Jacob D. , Rauscher Robert M. , Fritz Shayden R. , Fang Yayin , Billiot Eugene J. , Billiot Fereshteh H. , Morris Kevin F.
Published: June 2024

NMR spectroscopy, molecular modeling, and conductivity experiments were used to investigate micelle formation by the amino acid-based surfactant tridecanoic L-glutamic acid. Amino acid-based biosurfactants are green alternatives to surfactants derived from petroleum. NMR titrations were used to measure the monomeric surfactant’s primary and gamma (γ) carboxylic acid pKa values. Intramolecular hydrogen bonding within the surfactant’s headgroup caused the primary carboxylic acid to be less acidic than the corresponding functional group in free L-glutamic acid. Likewise, intermolecular hydrogen bonding caused the micellar surfactant’s γ carboxylic functional group to be less acidic than the corresponding monomer value. The binding of four positive counterions to the anionic micelles was also investigated. At pH levels below 7.0 when the surfactant headgroup charge was −1, the micelle hydrodynamic radii were larger (~30 Å) and the mole fraction of micelle-bound counterions was in the 0.4–0.7 range. In the pH range of 7.0–10.5, the micelle radii decreased with increasing pH and the mole fraction of micelle bound counterions increased. These observations were attributed to changes in the surfactant headgroup charge with pH. Above pH 10.5, the counterions deprotonated and the mole fraction of micelle-bound counterions decreased further. Finally, critical micelle concentration measurements showed that the micelles formed at lower concentrations at pH 6 when the headgroup charge was predominately −1 and at higher concentrations at pH 7 where headgroups had a mixture of −1 and −2 charges in solution.
Dual-Energy and Photon-Counting Computed Tomography in Vascular Applications—Technical Background and Post-Processing Techniques
Authors: Stański Marcin , Michałowska Ilona , Lemanowicz Adam , Karmelita-Katulska Katarzyna , Ratajczak Przemysław , Sławińska Agata , Serafin Zbigniew
Published: June 2024

The field of computed tomography (CT), which is a basic diagnostic tool in clinical practice, has recently undergone rapid technological advances. These include the evolution of dual-energy CT (DECT) and development of photon-counting computed tomography (PCCT). DECT enables the acquisition of CT images at two different energy spectra, which allows for the differentiation of certain materials, mainly calcium and iodine. PCCT is a recent technology that enables a scanner to quantify the energy of each photon gathered by the detector. This method gives the possibility to decrease the radiation dose and increase the spatial and temporal resolutions of scans. Both of these techniques have found a wide range of applications in radiology, including vascular studies. In this narrative review, the authors present the principles of DECT and PCCT, outline their advantages and drawbacks, and briefly discuss the application of these methods in vascular radiology.
High-Frequency Vestibular Function Is Vulnerable to Presbyvestibulopathy
Authors: Bae Seonghoon , Yun Jimin , Kwak Seungmin , Jung Hyuntaek , Lee Hancheol , Kim Juyoung , Kim Chanhee , Lee Yujin , Kim Sunghuhn
Published: June 2024

Introduction: In 2019, mild vestibular function deficiency in elder populations was defined as presbyvestibulopathy (PVP) by the Classification Committee of the Bárány Society. The diagnostic criteria include tests for low-, mid-, and high-frequency vestibular function, represented by caloric testing, rotary chair testing, and head impulse testing, respectively. However, there is still a lack of large-scale reports supporting the relationship between vestibular function tests (VFTs) and aging. In this study, we evaluated whether each test is correlated with aging in the elderly population aged over 50. Methods: This study retrospectively enrolled 1043 subjects from a single university hospital database after excluding those with unilateral and bilateral vestibulopathy, central dizziness, and acute dizziness. Enrolled subjects had caloric canal paresis <20%, vHIT lateral canal gain >0.6, vHIT interaural difference <0.3, and age >50 years old. Results: Significant negative correlations with age were identified in the vHIT (p < 0.001) and rotary chair test (RCT) 1.0 Hz gain (p = 0.030). However, the caloric test (p = 0.739 and 0.745 on the left and right sides, respectively) and RCT 0.12 Hz gain (p = 0.298) did not show a significant correlation with age. A total of 4.83% of subjects aged 70 years or older showed sub-normal vHIT gain that met the criteria of PVP, whereas only 0.50% of subjects aged 60 to 69 did. The prevalence of sub-normal caloric test results, however, was not significantly different between the two age groups (21.55% in the 60–69 age group and 26.59% in the >70 age group). Conclusions: The high-frequency range vestibular function seems vulnerable to aging, and this is more discernible at age >70 years. The weak correlation between age and low-frequency vestibular function tests, such as the caloric test and low-frequency rotary chair testing, suggests the need to revisit the diagnostic criteria for PVP.