bluuebunny/crossref_metadata_2025 huggingface dataset:
Mood Stabilizers of First and Second Generation
Authors: Rybakowski Janusz K.
Published: May 2023

The topic of this narrative review is mood stabilizers. First, the author’s definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author’s criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with “insufficient” ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided.
Application of Pseudo-Three-Dimensional Residual Network to Classify the Stages of Moyamoya Disease
Authors: Xu Jiawei , Wu Jie , Lei Yu , Gu Yuxiang
Published: May 2023

It is essential to assess the condition of moyamoya disease (MMD) patients accurately and promptly to prevent MMD from endangering their lives. A Pseudo-Three-Dimensional Residual Network (P3D ResNet) was proposed to process spatial and temporal information, which was implemented in the identification of MMD stages. Digital Subtraction Angiography (DSA) sequences were split into mild, moderate and severe stages in accordance with the progression of MMD, and divided into a training set, a verification set, and a test set with a ratio of 6:2:2 after data enhancement. The features of the DSA images were processed using decoupled three-dimensional (3D) convolution. To increase the receptive field and preserve the features of the vessels, decoupled 3D dilated convolutions that are equivalent to two-dimensional dilated convolutions, plus one-dimensional dilated convolution, were utilized in the spatial and temporal domains, respectively. Then, they were coupled in serial, parallel, and serial–parallel modes to form P3D modules based on the structure of the residual unit. The three kinds of module were placed in a proper sequence to create the complete P3D ResNet. The experimental results demonstrate that the accuracy of P3D ResNet can reach 95.78% with appropriate parameter quantities, making it easy to implement in a clinical setting.
Sexual Dysfunction in Multiple Sclerosis: The Role of Executive Function
Authors: Marinetto Silvia , Riccardi Alice , Barbadoro Filippo , Pucci Veronica , Selini Enrico , Pavan Aghite , Rinaldi Francesca , Perini Paola , Puthenparampil Marco , Gallo Paolo , Mondini Sara
Published: May 2023

Cognitive impairment and sexual dysfunction are common symptoms in persons with Multiple Sclerosis (MS). The present study focuses on the relationship between these two dimensions by means of a specific assessment commonly used in clinical practice with this population. Fifty-five persons with a diagnosis of MS underwent specific cognitive tests and answered clinical questionnaires. Two cognitive tests, one for memory (the Selective Reminding Test), and one for attention (the Symbol Digit Modalities Test), were administered together with two tests for executive functions (the D-KEFS Sorting Test and Stroop Test). Two self-report questionnaires to investigate clinical, psychological and sexual features (the Beck Depression Inventory-II and Self-perception of Cognition in Multiple Sclerosis and Multiple Sclerosis Intimacy and Sexuality Questionnaire-19), were also administered. The main result highlights that sexual difficulties are associated with cognitive deficits, particularly with executive disorders, but not with memory and attention. Furthermore, sexual difficulties are better explained when depression symptoms are also taken into account. This study disentangles the interaction between sexual dysfunction, cognitive impairment and depression in persons with MS by emphasising the role of very high cognitive processing (i.e., executive functioning) in determining human behaviour.
The Effect of Preload Loss on the Mechanical Properties of Grid Structure Connected with Bolted-Ball Joints
Authors: Pan Zuanfeng , Wang Hao , Yang Yichao , Li Wendi , Shang Jiaqi , Gu Zhengyu
Published: May 2023

Bolt-ball joints are widely adopted in grid structures due to their high installation accuracy and short construction period. Since the bolt is inside the joint, it is challenging to evaluate its health status from outside the structure. A finite-element plane-truss structure model, based on the actual grid structure, was constructed to investigate the influence of the rod’s preload on the overall stiffness and bearing capacity of the grid structure. Moreover, a model of the grid structure, with a bolt-ball joint connection, was constructed to analyze the influence of the preload loss in bolted-ball joints on the overall mechanical performance of the local members and structures. The results show that the release of preload on the outer web rod is less effective in terms of the overall stiffness and bearing capacity of the structure than on the inner web rod. The preload of the larger span direction rod plays an important role, and the preload of the upper chord has a greater impact, while the preload of the web rod and the upper chord in the smaller span direction has no significant effect on the normal stress in the surrounding rods.
Modelling and Multi-Objective Optimisation of Finger Joints: Improving Flexural Performance and Minimising Wood Waste
Authors: Le Son Tay , Nguyen Tuan Ngoc , Bui Dac-Khuong , Ha Quang Phuc , Ngo Tuan Duc
Published: May 2023

The wood industry faces the dual requirements of improving the quality of timber products and minimising waste during the manufacturing process. The finger joint, which is an end-to-end joining method for timber boards, is one of the most important aspects of engineering wood products. This study presents a numerical and optimisation investigation of the effects of finger-joint design parameters on the flexural behaviour of finger-jointed timber beams. A numerical model based on advanced three-dimensional finite element analysis was developed to model the behaviour of finger-jointed beams. Using the validated finite element (FE) model and automated parameterisation, a parametric study was conducted to assess the impact of each design parameter of the finger joint, including finger length, tip thickness, and the number of finger joints. The results indicate that the number of fingers and finger length significantly influence the maximum load capacity, while the tip thickness has a marginal effect on performance. This study identifies a design threshold of five fingers and a 14 mm finger length for achieving efficient, high-performance finger-joint designs. In addition, the multi-objective modified firefly algorithm (MOMFA) was proposed to maximise the finger joint resistance while simultaneously minimising the material waste. The optimisation shows that there will be a significant amount of wood waste when using traditional single-objective optimisation that only focuses on structural performance. In contrast, the proposed method achieves comparable load capacity while significantly reducing waste (up to 53.31%) during the joining process. The automated finite element modelling framework and holistic optimisation developed in this study can be used to design and optimise engineering wood products for construction applications.
An Integrated Framework for Preservation of Hawaii Indigenous Culture: Learning from Vernacular Knowledge
Authors: Hu Ming , Suh Junghwa , Pedro Camryn
Published: May 2023

Vernacular architecture represents the traditional architecture that developed over time within a particular culture or region that embodied indigenous knowledge. These buildings provide an invaluable cultural heritage, and learning from them is an important way to preserve indigenous culture. However, the negative view commonly held about indigenous knowledge in architectural theory and historical research that developed during the colonial era has not begun to change; the indigenous knowledge embedded in vernacular architecture has been ignored. This article discusses a proposed framework in which we can learn from vernacular architecture to preserve indigenous culture, including studying traditional building techniques, incorporating traditional materials and designs, adapting traditional designs to contemporary needs, involving local communities, and encouraging sustainable building practices. This proposed framework is applied to learning from Native Hawaiian architecture as a way to demonstrate its practicality and necessity. By studying the designs, materials, and techniques used in vernacular buildings, we can gain a deeper understanding of the cultural, environmental, and social contexts in which they were created.
Shear Behavior of Geopolymer Concrete Slender Beams
Authors: Tauqir Muhammad , Qazi Asad Ullah , Khan Qasim S. , Munir Muhammad Junaid , Kazmi Syed Minhaj Saleem
Published: May 2023

This study investigates the shear behavior of slender steel-reinforced geopolymer concrete (GPC) beams with the shear span to effective depth ratio (a/d) of 4.5 and 5.0. To investigate the effect of shear reinforcement, two ordinary Portland cement concrete (OPC) beams and two GPC beams without shear reinforcement, and two OPC beams and two GPC beams reinforced with shear stirrups were cast. All beams were 150 mm wide and 225 mm deep with lengths of 1770 mm (a/d=4.5) and 1950 mm (a/d=5). The beams were tested under a three-point bending test. The experimental results showed that OPC and GPC beams without and with shear reinforcements exhibited similar crack propagation and failure mechanism. The midspan deflections of GPC beams were greater than OPC beams. The normalized shear resistance of OPC and GPC beams with a/d ratio 4.5 was greater than 4% and 30%, respectively, than beams with a/d ratio 5. OPC beams showed a greater decrease in shear resistance with an increasing a/d ratio compared to GPC beams. The shear resistances computed using empirical relationships available in various OPC design codes including AC1-318-14, AC1-318-19, fib-10 and JSCE-07 underestimated the experimental shear resistance of both OPC and GPC beams. In addition, the environmental assessment of OPC and GPC beams exhibited that GPC beams emit about 34% lower embodied CO2 emissions than OPC beams.
Metal–Organic Frameworks (MOFs) Based Electrospun Nanofiber Membrane for Passive Indoor Moisture Control
Authors: Ding Dong , Qin Menghao
Published: May 2023

Metal–organic frameworks (MOFs), an emerging class of porous sorbents, have become one of the most promising functional materials for indoor moisture regulation. However, the practical application of MOFs in building environments is challenging. Common shaping forms of MOFs (e.g., pellets, tablets, monoliths, granules, coating, etc.) may lead to agglomeration of MOF particles, higher usage costs, low efficiency, and material waste. Here, we report a new MOF-based electrospun nanofiber membrane with high porosity, light weight, and a large surface-area-to-volume ratio. MOF nanoparticles distributed on the fibers can fully contact moisture in the air, thus significantly enhancing MOFs’ utilization and performance. The results of the moisture adsorption test show that the improved MOF membrane has significantly higher water vapor uptake than most conventional hygroscopic materials and textiles in built environments. A building energy model was established to evaluate the MOF membrane’s effect on building energy consumption under different climates worldwide. The simulation results show that the MOF membrane can efficiently moderate indoor moisture fluctuation and has excellent energy-saving potential. The latent heat load reduction rate in summer can be up to 80–90% in arid/semi-arid climates and around 50% in temperate climates in a purely passive manner.
Analysis of Performance Strategies for the Preservation of Heritage Buildings: The Case of Puerto de Santa María
Authors: Castilla Manuel V.
Published: May 2023

Adverse impacts of industrial constructions have been central to debates on sustainable development and this issue is partly due to that the building sector is highly demanding in relation to energy efficiency. The future of an industrial building, given to its link with the production process, is also connected to the activity itself. In this sense, the conservation of the original industrial activity of a wine cellar construction requires very specific values of several microclimate parameters. The accurate modelling of these values is a key tool for analysing the performance of this building typology. The main goal of this paper is to present an integrated methodology to assess and optimize the efficiency and indoor microclimate for evaluating the potential of heritage buildings and acknowledge their features for future opportunities. The integrated model proposed is based on different assessments, which are the essential benchmarks of these buildings. This approach could be also proposed to any other heritage category to evaluate, according to several parameters and aspects, the preservation of its original activity. Due to the importance of natural light in this type of construction, the article presents an application able to simulate and analyse this fundamental aspect of an old winery with the use of advanced simulation tools.
A Perspective on AI-Based Image Analysis and Utilization Technologies in Building Engineering: Recent Developments and New Directions
Authors: Paduano Ivan , Mileto Andrea , Lofrano Egidio
Published: May 2023

Artificial Intelligence (AI) is a trending topic in many research areas. In recent years, even building, civil, and structural engineering have also started to face with several new techniques and technologies belonging to this field, such as smart algorithms, big data analysis, deep learning practices, etc. This perspective paper collects the last developments on the use of AI in building engineering, highlighting what the authors consider the most stimulating scientific advancements of recent years, with a specific interest in the acquisition and processing of photographic surveys. Specifically, the authors want to focus both on the applications of artificial intelligence in the field of building engineering, as well as on the evolution of recently widespread technological equipment and tools, emphasizing their mutual integration. Therefore, seven macro-categories have been identified where these issues are addressed: photomodeling; thermal imaging; object recognition; inspections assisted by UAVs; FEM and BIM implementation; structural monitoring; and damage identification. For each category, the main new innovations and the leading research perspectives are highlighted. The article closes with a brief discussion of the primary results and a viewpoint for future lines of research.
Urban Residents’ Preferred Walking Street Setting and Environmental Factors: The Case of Chengdu City
Authors: Yan Qian , Luo Shixian , Jiang Jiayi
Published: May 2023

To date, most studies on building environments and walking behavior have utilized top-down approaches (e.g., big data or social media data) yet lack bottom-up approaches to verify their findings. Therefore, this study divided urban streets into three main settings (community streets, waterfront paths, and urban greenways) and collected data from a sample of 411 urban residents in Chengdu via an online questionnaire to examine the impact of street environmental factors on their choice of walking path. It was found that: (1) people with higher levels of education preferred streets with water bodies as walking paths; (2) the environmental quality of the physical and aesthetic aspects both had an impact on residents’ choices, and the aesthetic environmental quality had a stronger impact; (3) the impact of most infrastructures on community streets was stronger than on other streets; (4) residents were more concerned about the environmental quality of waterfront paths and urban greenways. Based on these findings, three design patterns for residents’ preferred street environments are proposed.
Research on the Barriers and Strategies to Promote Prefabricated Buildings in China
Authors: Wang Qiankun , Shen Chuxiong , Guo Zeng , Zhu Ke , Zhang Jiaji , Huang Mei
Published: May 2023

Prefabricated buildings have the characteristics of being energy saving, protecting the environment, being labor saving and having a fast construction speed, which meet the requirement for the sustainable development of the construction industry and are been strongly supported by the country. However, the promotion of prefabricated buildings in China is still in its infancy, with numerous barriers, and the correlation between these factors is not well tested. Therefore, the objective of this study was to identify the main obstacles to the promotion of prefabricated buildings, clarify the correlation between the main barriers and classify them, so as to propose targeted promotion strategies. Combined with the PEST theory and the technology–organization–environment framework, this study has established a list of 27 barriers including policy, the economy, society, technology and management, through a literature review. Experts were invited to complete a questionnaire survey to assess the relative importance of barriers, and 15 major barriers were identified based on the analytic hierarchy process method. We conducted semi-structured interviews, determined the direct relationship between various barriers, established the adjacency matrix and calculated the reachability matrix, established the multi-level hierarchical structure model based on interpretative structural modeling, used Matrices Impacts Croises–Multiplication Appliance Classement to classify factors, and then proposed the industry–organization–project three-level promotion strategy according to the classification results. The results showed that technical factors accounted for the largest proportion in the list of barriers, followed by society, the economy, political factors and, finally, management factors. The main obstacles to the popularization of prefabricated buildings can be divided into three categories: autonomous variables, dependent variables and driver variables. It is necessary to put forward countermeasures from different dimensions to promote the application of prefabricated buildings. This study provides a practical reference for future research, attempts to provide solutions to promote the popularization of prefabricated buildings and also provides methodological guidance for similar research.
The Unintended Consequences of COVID-19 Economic Responses on First Home Buyers? Evidence from New South Wales, Australia
Authors: Bangura Mustapha , Lee Chyi Lin , Schafer Benjamin
Published: May 2023

As in many other nations, the Australian Government implemented monetary and fiscal policies in response to the COVID-19 pandemic to aid economic recovery. Among these policies were specific measures to assist first home buyers (FHBs) in entering the housing market. However, these unprecedented economic policies might have other direct and indirect implications on FHBs, which have yet to be thoroughly explored in the literature. To fill this gap, through a survey, we collected information via public and online mortgage broker platforms from 61 FHBs who successfully entered the housing market or were actively searching during the pandemic. The results found COVID-19 economic responses counterproductive for FHBs, pushing them to a more disadvantaged position due to an overheated property market. In addition, since the onset of the pandemic, property prices have risen significantly, exacerbating housing inequality as FHBs increasingly rely on intergenerational family support, take on more financial risk, and relocate to regional areas due to fear of missing out. The study highlights the need for macroeconomists and housing policymakers to consider these unintended consequences in formulating policies that minimise the adverse effects of economic stimulus measures.
Regioselective Esterification of Cardiac Glycosides Catalyzed by Novozym 435 and Lipase PS in Organic Solvents
Authors: Bassanini Ivan , Roncaglia Lucia , Danieli Bruno , Riva Sergio
Published: May 2023

The enzymatic acetylation in the organic solvents of a number of the important bioactive cardiac glycosides was investigated. With the bufanolide proscillaridin A and the cardenolide lanatoside C, acylation, as expected, occurred at the secondary 4′-OH of the rhamnopyranosyl unit of the former (by the action of Novozym 435 lipase) and the primary 6′′′′-OH of the terminal glucopyranosyl unit of the latter (best results obtained by the action of the lipase PS). Only lipase PS was found to be able to acylate the cardenolides digitoxin and digoxin at the 4‴-OH of their terminal digitoxose unit. The corresponding monoacetyl derivatives, both of which are commercialized drugs, could be isolated with good yields. The investigation of the Novozym 435-catalyzed acetylation of free D-digitoxose provided a possible explanation for the inability of this lipase to acylate digitoxin and digoxin.
Catalytical Performance of Heteroatom Doped and Undoped Carbon-Based Materials
Authors: Alom Jahangir , Hasan Md. Saif , Asaduzaman Md. , Alam Mohammad Taufiq , Belhaj Dalel , Selvaraj Raja , Hossain Md. Ashraf , Zargar Masoumeh , Ahmed Mohammad Boshir
Published: May 2023

Developing cost-effective, eco-friendly, efficient, stable, and unique catalytic systems remains a crucial issue in catalysis. Due to their superior physicochemical and electrochemical properties, exceptional structural characteristics, environmental friendliness, economic productivity, minimal energy demand, and abundant supply, a significant amount of research has been devoted to the development of various doped carbon materials as efficient catalysts. In addition, carbon-based materials (CBMs) with specified doping have lately become significant members of the carbon group, showing promise for a broad range of uses (e.g., catalysis, environmental remediation, critical chemical production, and energy conversion and storage). This study will, therefore, pay attention to the function of heteroatom-based doped and undoped CBMs for catalytical applications and discuss the underlying chemistries of catalysis. According to the findings, doping CBMs may greatly improve their catalytic activity, and heteroatom-doped CBMs may be a promising option for further metal doping to attach them to an appropriate place. This paper also covers the potential applications of both doped and undoped CBMs in the future.
The Semi-Closed Molten Salt-Assisted One-Step Synthesis of N-P-Fe Tridoped Porous Carbon Nanotubes for an Efficient Oxygen Reduction Reaction
Authors: Deng Jianghai , Zhou Qiuyun
Published: May 2023

Transition metal and heteroatom co-doped carbon nanomaterials (TM-H-C) are considered to be the most promising candidates to replace the expensive platinum-based catalysts for oxygen reduction reactions (ORR). Herein, we report a semi-closed molten salt-assisted one-step strategy for fabricating N-P-Fe-tridoped porous carbon nanotube (CNT) catalysts by using the evaporation of ZnCl2 and the catalysis of iron ions to control the heteroatoms doping process and CNT formation. The resultant densely packed porous CNT structure imparts final catalysts with an enhanced mass transfer ability for electron and ORR-involved species, ensuring a high performance in catalyzing the ORR. Significantly, the optimal catalysts show a half-wave potential of 0.89 V (vs. RHE), which is better than commercial platinum-based catalysts and most reported TM-H-C ORR catalysts. Impressively, when applied to a primary inc-oxygen (Zn–O2) battery, the synthesized catalyst comprehensively outperforms the state-of-the-art platinum-based catalyst in both its maximum power density and specific capacity.
Atmospheric and Efficient Selective Oxidation of Ethylbenzene Catalyzed by Cobalt Oxides Supported on Mesoporous Carbon Nitride
Authors: Zhu Ye , Zhang Xue-Wen , Wang Fei , Xue Bing , Xu Jie
Published: May 2023

Mesoporous carbon nitride (mpg-C3N4) was prepared by using cyanamide as a precursor and colloidal nanosilica as a template. Then, the mpg-C3N4 was used as a catalytic support to load CoOx. The physicochemical properties of the synthesized CoOx/mpg-C3N4 materials were elucidated by multiple characterization methods, and the catalytic activities were examined in the selective oxidation of ethylbenzene (EB) under atmospheric pressure by using tert-butyl hydrogen peroxide (TBHP) as an oxidant. It was found that mpg-C3N4 possessed a higher specific surface area than other carbon nitride materials, and its abundant Nb species were able to interact with Co (II) species. When the dosages of EB and TBHP were 10 mmol and 30 mmol, respectively, the reaction temperature was 100 °C, and the reaction time was 10 h, the conversion rate of ethylbenzene was 62%, and the selectivity of AP was 84.7%.
Optimization Study of Glucose Synthesis to 5-Hydroxymethylfurfural (5-HMF) by Using Low Transition-Temperature Mixtures (LTTM)
Authors: Abdul Manaf Aida Syafiqah , Mostapha Marhaini , Ameen Mariam , Yusup Suzana , Amran Nurul Aini
Published: May 2023

5-Hydroxymethylfurfural (5-HMF) is a potential value-added product gaining popularity due to its wide range of applications. Glucose is widely used for 5-HMF production because it is abundant and more cost-effective than other resources. In the current research, a combination of microwave irradiation and low transition-temperature mixture (LTTM) for 5-HMF production was sustainably created. A preliminary study was conducted to derive 5-HMF using LTTM as a green solvent in various ratios of glucose: LTTM (MA/ChCl): water (10:100:15) and (10:48:100) via microwave heating at 90 °C for 10–60 min reaction time. The product analysis revealed that the 10:100:15 combination ratio of glucose: LTTM: water produced more 5-HMF (20.5%) than the 10:48:100 (0.28%) ratio. Following the preliminary results, an optimization study was conducted, focusing on the reaction temperature, LTTM mass, and water to assess the impact on 5-HMF yield and glucose conversion, using CCD in Design-Expert software. The quadratic model fit for 5-HMF yield and the 2FI model for glucose conversion yielded R2 values of 0.9861 and 0.8610, respectively. Both responses had a significant p value of 0.0061 for glucose conversion and <0.0001 for 5-HMF yield. An optimum point was achieved at 100 °C, 100 g of LTTM, and 20 g of water, with an expected 5-HMF yield and glucose conversion of 45.77% and 69.03%, respectively.
Recent Achievements in the Copper-Catalyzed Arylation of Adamantane-Containing Amines, Di- and Polyamines
Authors: Averin Alexei D. , Panchenko Svetlana P. , Murashkina Arina V. , Fomenko Varvara I. , Kuliukhina Daria S. , Malysheva Anna S. , Yakushev Alexei A. , Abel Anton S. , Beletskaya Irina P.
Published: May 2023

Rapid development of the copper-catalyzed amination of aryl halides in the beginning of the 21st century, known as the Renaissance of the Ullmann chemistry, laid foundations for the use of this method as a powerful tool for the construction of the C(sp2)-N bond and became a rival of the Buchwald–Hartwig amination reaction. Various applications of this approach are well-documented in a number of comprehensive and more specialized reviews, and this overview in the form of a personal account of the Cu-catalyzed arylation and heteroarylation of the adamantane-containing amines, and di- and polyamines, covers a more specific area, showing the possibilities of the method and outlining general regularities, considering reagents structure, copper source and ligands, scope, and limitations. The material of the last decade is mainly considered, and recent data on the application of the unsupported copper nanoparticles and possibilities of the Chan-Lam reaction as an alternative to the use of aryl halides are also discussed.
Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19
Authors: Paunovic Verica , Vucicevic Ljubica , Misirkic Marjanovic Maja , Perovic Vladimir , Ristic Biljana , Bosnjak Mihajlo , Mandic Milos , Stevanovic Danijela , Harhaji-Trajkovic Ljubica , Lalosevic Jovan , Nikolic Milos , Bonaci-Nikolic Branka , Trajkovic Vladimir
Published: May 2023

As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
Selection of Cell Populations with High or Low Surface Marker Expression Using Magnetic Sorting
Authors: Polyakova Natalia , Kandarakov Oleg , Belyavsky Alexander
Published: May 2023

Magnetic cell sorting technology stands out because of its speed, simplicity, and ability to process large cell numbers. However, it also suffers from a number of drawbacks, in particular low discrimination power, which results in all-or-none selection outcomes limited to a bulk separation of cell populations into positive and negative fractions, as well as the modest purity of the selected cells and the inability to select subpopulations of cells with high expression of a surface marker. In the present study, we developed a simple solution to this problem and confirmed the effectiveness of this approach by multiple experiments with the magnetic selection of transduced cell populations. Murine NIH 3T3 cells were transduced with the bicistronic retroviral vector constructs co-expressing fluorescent reporter proteins EGFP (enhanced green fluorescent protein) or DsRed-Express 2 and LNGFR (low-affinity nerve growth factor receptor) as surface selection markers. The effects of the magnetic selection of transduced cells with anti-LNGFR Micro Bead (MB) doses ranging from 0.5 to 80 µL have been assessed. Low doses of MBs favored the depletion of weakly positive cells from the population, resulting in the higher expression levels of EGFP or DsRed-Express2 reporters in the selected cell fractions. Low MB doses also contributed to the increased purity of the selected population, even for samples with a low initial percentage of positive cells. At the same time, high MB doses resulted in the increased yield and a more faithful representation of the original expression profiles following selection. We further demonstrate that for populations with fairly narrow distribution of expression levels, it is possible to achieve separation into high- and low-expressing subsets using the two-stage selection scheme based on the sequential use of low and high doses of MBs. For populations with broad expression distribution, a one-stage selection with low or high doses of MBs is sufficient for a clear separation of low- and high-expressing subsets in the column-retained and flow-through fractions, respectively. This study substantially extends the potential of magnetic cell sorting, and may open new possibilities in a number of biomedical applications.
Concurrent Activation of Both Survival-Promoting and Death-Inducing Signaling by Chloroquine in Glioblastoma Stem Cells: Implications for Potential Risks and Benefits of Using Chloroquine as Radiosensitizer
Authors: Müller Andreas , Weyerhäuser Patrick , Berte Nancy , Jonin Fitriasari , Lyubarskyy Bogdan , Sprang Bettina , Kantelhardt Sven Rainer , Salinas Gabriela , Opitz Lennart , Schulz-Schaeffer Walter , Giese Alf , Kim Ella L.
Published: May 2023

Lysosomotropic agent chloroquine was shown to sensitize non-stem glioblastoma cells to radiation in vitro with p53-dependent apoptosis implicated as one of the underlying mechanisms. The in vivo outcomes of chloroquine or its effects on glioblastoma stem cells have not been previously addressed. This study undertakes a combinatorial approach encompassing in vitro, in vivo and in silico investigations to address the relationship between chloroquine-mediated radiosensitization and p53 status in glioblastoma stem cells. Our findings reveal that chloroquine elicits antagonistic impacts on signaling pathways involved in the regulation of cell fate via both transcription-dependent and transcription-independent mechanisms. Evidence is provided that transcriptional impacts of chloroquine are primarily determined by p53 with chloroquine-mediated activation of pro-survival mevalonate and p21-DREAM pathways being the dominant response in the background of wild type p53. Non-transcriptional effects of chloroquine are conserved and converge on key cell fate regulators ATM, HIPK2 and AKT in glioblastoma stem cells irrespective of their p53 status. Our findings indicate that pro-survival responses elicited by chloroquine predominate in the context of wild type p53 and are diminished in cells with transcriptionally impaired p53. We conclude that p53 is an important determinant of the balance between pro-survival and pro-death impacts of chloroquine and propose that p53 functional status should be taken into consideration when evaluating the efficacy of glioblastoma radiosensitization by chloroquine.
Engineered Synthetic STxB for Enhanced Cytosolic Delivery
Authors: Hadjerci Justine , Billet Anne , Kessler Pascal , Mourier Gilles , Ghazarian Marine , Gonzalez Anthony , Wunder Christian , Mabrouk Nesrine , Tartour Eric , Servent Denis , Johannes Ludger
Published: May 2023

Many molecular targets for cancer therapy are located in the cytosol. Therapeutic macromolecules are generally not able to spontaneously translocate across membranes to reach these cytosolic targets. Therefore a strong need exists for tools that enhance cytosolic delivery. Shiga toxin B-subunit (STxB) is used to deliver therapeutic principles to disease-relevant cells that express its receptor, the glycolipid Gb3. Based on its naturally existing membrane translocation capacity, STxB delivers antigens to the cytosol of Gb3-positive dendritic cells, leading to the induction of CD8+ T cells. Here, we have explored the possibility of further increasing the membrane translocation of STxB to enable other therapeutic applications. For this, our capacity to synthesize STxB chemically was exploited to introduce unnatural amino acids at different positions of the protein. These were then functionalized with hydrophobic entities to locally destabilize endosomal membranes. Intracellular trafficking of these functionalized STxB was measured by confocal microscopy and their cytosolic arrival with a recently developed highly robust, sensitive, and quantitative translocation assay. From different types of hydrophobic moieties that were linked to STxB, the most efficient configuration was determined. STxB translocation was increased by a factor of 2.5, paving the path for new biomedical opportunities.
Targeting Liver X Receptors for the Treatment of Non-Alcoholic Fatty Liver Disease
Authors: Kim Hyejin , Park Chaewon , Kim Tae Hyun
Published: May 2023

Non-alcoholic fatty liver disease (NAFLD) refers to a range of conditions in which excess lipids accumulate in the liver, possibly leading to serious hepatic manifestations such as steatohepatitis, fibrosis/cirrhosis and cancer. Despite its increasing prevalence and significant impact on liver disease-associated mortality worldwide, no medication has been approved for the treatment of NAFLD yet. Liver X receptors α/β (LXRα and LXRβ) are lipid-activated nuclear receptors that serve as master regulators of lipid homeostasis and play pivotal roles in controlling various metabolic processes, including lipid metabolism, inflammation and immune response. Of note, NAFLD progression is characterized by increased accumulation of triglycerides and cholesterol, hepatic de novo lipogenesis, mitochondrial dysfunction and augmented inflammation, all of which are highly attributed to dysregulated LXR signaling. Thus, targeting LXRs may provide promising strategies for the treatment of NAFLD. However, emerging evidence has revealed that modulating the activity of LXRs has various metabolic consequences, as the main functions of LXRs can distinctively vary in a cell type-dependent manner. Therefore, understanding how LXRs in the liver integrate various signaling pathways and regulate metabolic homeostasis from a cellular perspective using recent advances in research may provide new insights into therapeutic strategies for NAFLD and associated metabolic diseases.
A Machine Learning-Based Study of Li+ and Na+ Metal Complexation with Phosphoryl-Containing Ligands for the Selective Extraction of Li+ from Brine
Authors: Kireeva Natalia , Baulin Vladimir E. , Tsivadze Aslan Yu.
Published: May 2023

The growth of technologies concerned with the high demand in lithium (Li) sources dictates the need for technological solutions garnering Li supplies to preserve the sustainability of the processes. The aim of this study was to use a machine learning-based search for phosphoryl-containing podandic ligands, potentially selective for lithium extraction from brine. Based on the experimental data available on the stability constant values of phosphoryl-containing organic ligands with Li+ and Na+ cations at 4:1 THF:CHCl3, candidate di-podandic ligands were proposed, for which the stability constant values (logK) with Li+ and Na+ as well as the corresponding selectivity values were evaluated using machine learning methods (ML). The modelling showed a reasonable predictive performance with the following statistical parameters: the determination coefficient R2= 0.75, 0.87 and 0.83 and root-mean-square error RMSE = 0.485, 0.449 and 0.32 were obtained for the prediction of the stability constant values with Li+ and Na+ cations and Li+/Na+ selectivity values, respectively. This ML-based analysis was complemented by the preliminary estimation of the host–guest complementarity of metal–ligand 1:1 complexes using the HostDesigner software.
Perovskite-Structured NiTiO3 Modified NiO Gas Sensor for Xylene Detection
Authors: Qin Liyun , Gao Hongliang , Meng Fanli
Published: May 2023

Xylene gas is highly toxic, can irritate the skin, and is also very harmful to the body. Therefore, it is necessary to prepare sensors that can accurately detect xylene. In this paper, NiTiO3 nanoparticles were synthesized by the hydrothermal method and used to modify NiO, and a NiTiO3-modified NiO (NiTiO3-NiO) nanosheet material was successfully prepared. Its microstructure and internal composition were observed and analyzed by various characterization methods. When detecting 100 ppm xylene gas at the optimum temperature, comparing the response level of the NiTiO3-NiO sensor with that of a pure nickel oxide sensor, the former was 20 times that of the latter, and the sensitivity was greatly improved. In a 100 ppm xylene gas environment, the response level of the sensor reached 21, the minimum detection limit was 1 ppm, and the recovery time was 135.75 s. NiTiO3 is a perovskite-structured material, with many active sites and good catalytic properties that promote redox reactions.
Distinctive Labeling of Live Monocytes and Neutrophils with a Single Fluorescent Molecule
Authors: Kim Songhui , Fukuda Masahiro , Lee Jung Yeol , Chang Young-Tae , Je H. Shawn , Kim Beomsue
Published: May 2023

(1) Background: a small-molecule fluorescent chemosensor, CDr20, tracks the resident macrophages based on the UGT1A7C activity in the brain, raising the possibility that additional immune cells expressing the UGT1A7C can be labeled with CDr20. (2) Methods: we applied CDr20 to various types of blood cells derived from hematopoietic organs (spleen and bone marrow) as well as peripheral blood to test the degree and selectivity of labeling of CDr20 in these cell types; (3) Results: CDr20 fluorescently labels monocytes/macrophages and neutrophils as a result of glucuronidation reaction (CDr20-Gluc), which is mediated with UGT1A7C. The selectivity of CDr20 labeling highly correlates with the Ugt1a7c expression level in immune cells. Moreover, CDr20-Gluc is exported from cells by a mechanism of how glucuronides within cells are excreted into extracellular space. Interestingly, the exportation of CDr20-Gluc is mainly observed in monocytes, potentially due to the monocyte-specific expression of ABCC transporters and this resulted in large differences in the degree of fluorescence retention in neutrophils (CDr20bright), compared to monocytes (CDr20dim) upon one hour of CDr20 incubation; (4) Conclusions: CDr20 can differentially label monocytes and neutrophils due to the variance in two different cellular enzymatic activities of UGT1A7C and ABCC. By using this property, CDr20 can be used to distinguish specific cell types within blood.
Simulating the Detection of Dioxin-like Pollutants with 2D Surface-Enhanced Raman Spectroscopy Using h-BNC Substrates
Authors: Alvarado Raúl , Otero Nicolás , Mandado Marcos , Ramos-Berdullas Nicolás
Published: May 2023

The ability of 2D hybrid structures formed by boron, nitrogen and carbon atoms (h-BNCs) to act as potential substrates for the surface-enhanced Raman spectroscopy (SERS) detection of dioxin-like pollutants is theoretically analyzed. The strong confinement and high tunability of the electromagnetic response of the carbon nanostructures embedded within the h-BNC sheets point out that these hybrid structures could be promising for applications in optical spectroscopies, such as SERS. In this work, two model dioxin-like pollutants, TCDD and TCDF, and a model h-BNC surface composed of a carbon nanodisk of ninety-six atoms surrounded by a string of borazine rings, BNC96, are used to simulate the adsorption complexes and the static and pre-resonance Raman spectra of the adsorbed molecules. A high affinity of BNC96 for these pollutants is reflected by the large interaction energies obtained for the most stable stacking complexes, with dispersion being the most important contribution to their stability. The strong vibrational coupling of some active modes of TCDF and, specially, of TCDD causes the static Raman spectra to show a ”pure” chemical enhancement of one order of magnitude. On the other hand, due to the strong electromagnetic response of BNC96, confined within the carbon nanodisk, the pre-resonance Raman spectra obtained for TCDD and TCDF display large enhancement factors of 108 and 107, respectively. Promisingly, laser excitation wavelengths commonly used in SERS experiments also induce significant Raman enhancements of around 104 for the TCDD and TCDF signals. Both the strong confinement of the electromagnetic response within the carbon domains and the high modulation of the resonance wavelengths in the visible and/or UV region in h-BNCs should lead to a higher sensitivity than that of graphene and white graphene parent structures, thus overcoming one of the main disadvantages of using 2D substrates for SERS applications.
Printable and Flexible Iridium Oxide-Based pH Sensor by a Roll-to-Roll Process
Authors: Chawang Khengdauliu , Bing Sen , Chiao Jung-Chih
Published: May 2023

A flexible pH sensor based on using iridium oxide (IrOx) as the sensing film was developed by the roll-to-roll (R2R) process. The inert and biocompatible properties of IrOx make it a desired metal oxide for pH-sensing applications. The flexible substrates being continuously processed by the R2R technique provides the advantages of scalability, reconfigurability, resiliency, on-demand manufacturing, and high throughput, without the need for vacuum systems. Potential sweeps by cyclic voltammetry across the IrOx film against commercial and planar Ag/AgCl electrodes validated the reversible electrochemical mechanisms. Multiple IrOx electrodes showed similar output potentials when continuously tested in the pH range of 2–13, indicating good fabrication uniformity. For practical applications, planar IrOx/Ag-AgCl pairs developed on polyimide substrates were tested, with a good linear fit within pH 2–13, achieving Nernstian responses of around −60.6 mV/pH. The pH sensors showed good repeatability when analyzed with hysteresis, drift, fluctuation, and deviation as the stability factors. The selectivity of the interference ions and the effect of temperature were studied and compared with the reported values. The electrodes were further laminated in a process compatible with the R2R technique for packaging. The flexible sensors were tested under flat and curved surface conditions. Tests in artificial sweat and viscous solutions were analyzed in the Clarke error grid, showing reliable pH-sensing performance. The materials used during the manufacturing processes were sustainable, as the active materials were in small amounts and there was no waste during processing. No toxic chemicals were needed in the fabrication processes. The cost-effective and efficient materials and the fabrication process allow for rapid production that is necessary for disposable and point-of-care devices. Flexible electronics provide a platform for device and sensor integration and packaging, which enables Internet-of-things (IoT) network applications.