Proper Structure Research Articles

Non-lytic spread of poliovirus requires the nonstructural protein 3CD.

Non-enveloped viruses like poliovirus (PV) have evolved the capacity to spread by non-lytic mechanisms. For PV, this mechanism exploits the host secretory autophagy pathway. Virions are selectively incorporated into autophagosomes, double-membrane vesicles that travel to the plasma membrane, fuse, and release single-membrane vesicles containing virions. Loading of cellular cargo into autophagosomes relies on direct or indirect interactions with microtubule-associated protein 1B-light chain 3 (LC3) that are mediated by motifs referred to as LC3-interaction regions (LIRs). We have identified a PV mutant with a severe defect in non-lytic spread. An F-to-Y substitution in a putative LIR of the nonstructural protein 3CD prevented virion incorporation into LC3-positive autophagosomes and virion trafficking to the plasma membrane for release. Using high-angle annular dark-field scanning transmission electron microscopy to monitor PV-induced autophagosome biogenesis, for the first time, we show that virus-induced autophagic signals yield normal autophagosomes, even in the absence of virions. The F-to-Y derivative of PV 3CD was unable to support normal autophagosome biogenesis. Together, these studies make a compelling case for a direct role of a viral nonstructural protein in the formation and loading of the vesicular carriers used for non-lytic spread that may depend on the proper structure, accessibility, and/or dynamics of its LIR. The studies of PV 3CD protein reported here will hopefully provoke a more deliberate look at the presence and function of LIR motifs in viral proteins of viruses known to use autophagy as the basis for non-lytic spread.

Ergosterol Biosynthesis and Regulation Impact the Antifungal Resistance and Virulence of Candida spp.

Ergosterol is a key fungal sterol that is mainly found in the plasma membrane and is responsible for the proper membrane structure, rigidity, permeability and activity of membrane proteins. Ergosterol plays a crucial role in the ability of fungi to adapt to environmental stresses. The biosynthesis of ergosterol is also intimately connected with the antifungal resistance and virulence of pathogenic fungi. The most common etiological agents of life-threatening fungal infections are yeasts belonging to the genus Candida. The antifungal agents mostly used to treat Candida spp. infections are azoles, which act as competitive inhibitors of sterol demethylase, a key enzyme in the fungal ergosterol biosynthetic pathway. Although most studies on ergosterol biosynthesis, its regulation and the uptake of sterols are from the baker’s yeast Saccharomyces cerevisiae, the study of ergosterol biosynthesis and its relationship to antifungal drug resistance and virulence in pathogenic fungi is of utmost importance. The increasing antifungal drug resistance of Candida spp. and the limited armamentarium of antimycotics pose a challenge in the development of new therapeutic approaches. This review summarizes the available data on ergosterol biosynthesis and related phenomena in Candida albicans and non-albicans Candida species (Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida auris) with special emphasis on C. albicans and C. glabrata as the most common etiological agents of systemic candidiasis.

The Use of Picture Series of Central Kalimantan Folklore as a Visual Media in Teaching Writing of Narative Text

The objective of this research was to determine whether the use of picture series could improve the generic structure of students' writing, specifically their ability to write narrative texts with proper generic structure. The researcher employed a pre-experimental design with a one-group pre-test and post-test format. The population consisted of ninth-grade students from SMP Negeri 14 Palangka Raya during the 2023/2024 academic year, comprising three classes. The sample size was 30 students from class IX-A. The research findings indicated that using picture series improved students' writing abilities in terms of generic structure, particularly in writing narrative texts. This was evidenced by the increase in students’ mean scores from 60.9 in the pre-test to 81.8 in the post-test, reflecting 20.9 points of improvement. After calculating the difference between the matched pairs, the t-test value was found to be 9.390. With a significance level (p) = 0.05 and a degree of freedom (df) = 29, the t-table value was 1.699. Since the t-test value was greater than the t-table value (9.390 > 1.699), the null hypothesis (Ho) was rejected, and the alternative hypothesis (Ha) was accepted.

Exploring the theoretical potential of tungsten oxide (WOx) as a universal electron transport layer (ETL) for various perovskite solar cells through interfacial energy band alignment modulation

Perovskite solar cells (PSCs) play a pivotal role in advancing renewable energy to achieve United Nation's Sustainable Development Goal 7 (SDG 7), which aims to ensure universal access to affordable, sustainable, reliable and modern energy services. Aiming to enhance the performance of PSCs by replacing the typically used electron transport layers (ETLs: TiO2, SnO2, ZnO etc.), we theoretically investigated the viability of tungsten oxide (WOX) as a promising ETL for PSCs. Moreover, the effect of altering the energy levels of WOX on cell performance has also been analyzed through simulation. Initially, 12 (twelve) PSC structures having the combination of different perovskite (PSK: CsPbBr3, CsPbI3, FAPbBr3, FAPbI3) absorber layers with different organic hole transport layers (HTLs: Spiro-OMeTAD, P3HT, PEDOT:PSS) and a fixed ETL of WOX were optimized numerically for comparing their performance. As CsPbBr3-based PSCs showed the best performance, further simulations were performed by varying some WOX/CsPbBr3 interface properties such as interface defect density, conduction band offset (CBO) between WOX and CsPbBr3, energy bandgap (Eg) of WOX etc. Finally, the best-performed PSCs were found for the Eg = 3.5 eV of WOX and the CBO of - 0.5 eV confirming the conduction band minimum (CBM) of WOX is lower than that of CsPbBr3 by 0.5 eV. A properly chosen WOX layer enhanced the efficiency of CsPbBr3-based PSCs up to 14.65 %, 14.52 % and 16.09 %, aproaching the Shockley-Queisser (S-Q) limit (16.37% for CsPbBr3-based solar cell) from the initial values of 11.39 %, 11.27 %, and 12.49 %, respectively. This study ensures WOX is a promising ETL for which a proper PSC structure having a suitable PSK and an HTL can improve cell performance. Moreover, the importance of modifying energy levels of ETL material in enhancing the performance of PSCs is explored. As a result, this study opens a path for the researchers to develop WOX having suitable CBM and Eg, so that it can be well-suited with a properly matched PSK material resulting in enhanced cell performance.

High-quality femtosecond laser cutting of battery electrodes with enhanced electrochemical performance by regulating the taper angle: Promoting green manufacturing and chemistry

Laser cutting electrode technology is an environmentally friendly and sustainable manufacturing method that offers many benefits, such as low energy consumption and greenhouse gases, no waste production, no tool wear, flexible manipulation, and multi-scale processing. However, achieving high cutting quality with adjustable notch shape and controllable dimension precision is still a cutting-edge challenge. In addition, the influence of laser cutting on the microscopic structure and electrochemical performance of battery electrodes has not been fully illustrated. Here, the Li4Ti5O12 (LTO) electrode is cut using a femtosecond laser technology. The processing parameters are systematically optimized, and the influence of laser cutting taper structure on the structure and performance of LTO electrodes is comprehensively investigated. It is found that laser photoionization and the generated plasma could create oxygen vacancies and thus more Ti3+/Ti4+ defects in the LTO electrodes, resulting in increased electronic conductivity. Moreover, proper taper structure could help improve electrolyte infiltration as well as Li+ diffusion kinetics. As a result, the laser cutting LTO electrode with the optimized taper angle of T = 0.004 shows excellent electrochemical performance. The capacity retention is more than 99.2 % after 400 cycles at 1C, and the specific capacity reaches ∼60 mAh g−1 at a high rate of 60C, which is about 1.7 times higher than that of mechanically cutting LTO electrodes. The outstanding electrochemical performance is also demonstrated by LiFePO4||Li4Ti5O12 full cells. This work could pave the way for the development and application of laser technology in cutting battery electrodes.

The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6). However, the molecular mechanism by which the capsid promotes reverse transcription is undefined. Here we show that wild type HIV-1 virions can undergo efficient reverse transcription in vitro in the absence of a membrane-permeabilizing agent. This activity, originally termed "natural endogenous reverse transcription" (NERT), depends on expression of the viral envelope glycoprotein during virus assembly and its incorporation into virions. Truncation of the gp41 cytoplasmic tail markedly reduced NERT activity, suggesting that gp41 licenses the entry of nucleotides into virions. By contrast to reverse transcription in permeabilized virions, NERT required neither the addition of IP6 nor a mature capsid, indicating that an intact viral membrane can substitute for the function of the viral capsid during reverse transcription in vitro. Collectively, these results demonstrate that the viral capsid functions as a nanoscale container for reverse transcription during HIV-1 infection.

THE POETICS OF UTOPIA IN THE WORKS OF A. V. CHAYANOV

The futurological model presented in “My brother Alexei’s Journey to the Land of Peasant Utopia” by A. V. Chayanov (under the name of Iv. Kremnev) is focused on preserving and reviving the traditions of the times past, which are harmoniously integrated into a new way of life. The utopian worldview is very eclectic: along with manual agricultural labor, there are the latest inventions: meteorophores and aircraft, atmospheric precipitation is controlled. Art as a philosophical imperative defines all aspects of society. The leaders of the state, rely on the achievements of eugenics, striving to maximize the realization of each person’s talent, education is based on the principles of harmonious personal development: utopia’s residents not only master a specialty, but must know the history of art, play sports, which should also serve to reveal their abilities. The ideal is formed by both the ancient culture and manor pastime, where a person works in close contact with nature, spending leisure time in literary or musical pursuits. Knowledge of history and art is considered fundamental here: even cooking and entertainment are focused on preserving the memory of the past. Many of the ideas on which utopia is based are Chayanov’s ideas about the proper structure of education, its cultural and art history components, pedagogical and methodological principles, and the formation of a versatile and multifaceted scientist. But in a way, it is also an answer to the disputes of the late 19th — early 20th centuries about the role of man as a theurgist, the limits of his capabilities and power.

Faecal microbiota transplantation associated adverse events

Abstract Faecal microbiota transplantation (FMT) aims to restore intestinal microbiota balance with the objective of normalising its composition and achieve therapeutic benefits. The procedure involves the administration of fresh or frozen faecal microbes from a healthy donor into the recipient’s gastrointestinal tract with the intent to restore the proper structure and functionality of the recipient’s intestinal microbial community. Evidence showing the positive effects of FMT is abundant, however, less attention has been devoted to FMT-associated adverse events, especially in relation to liver diseases. Based on literature review, studies and reports regarding FMT-associated adverse events since the beginning of FMT use, have been analysed. The review covering the period 2010-2022 was undertaken in accordance with the PRISMA guidelines. Studies conducted on the patient population suffering from various types and forms of liver disease have proven the possible effectiveness of the FMT method and reported moderate adverse events (nausea, constipation, flatulence). Severe adverse events occurring in relation to FMT were also noted. No safety issues or infection signals associated with FMT were observed in studies performed within the population suffering from cirrhosis. The present review of scientific reports, publications and literature reviews describes the adverse events reported in the literature. Faecal microbiota transplants are associated with adverse events classified as mild, moderate and severe, among others, diarrhoea, fever, infections or death. There is a need to implement a donor screening programme and personalised transplantation methods. Further research is recommended to assess and monitor FMT efficacy, benefits and risks.

GTC: GNN-Transformer co-contrastive learning for self-supervised heterogeneous graph representation

Graph Neural Networks (GNNs) have emerged as the most powerful weapon for various graph tasks due to the message-passing mechanism’s great local information aggregation ability. However, over-smoothing has always hindered GNNs from going deeper and capturing multi-hop neighbors. Meanwhile, most methods follow a semi-supervised learning manner, the label scarcity would limit their applicability in real-world systems. Unlike GNNs, Transformers can model global information and multi-hop interactions via multi-head self-attention and a proper Transformer structure can show more immunity to over-smoothing. So, can we propose a novel framework to combine GNN and Transformer, integrating both GNN’s local information aggregation and Transformer’s global information modeling ability to eliminate the over-smoothing problem and achieve self-supervised graph representation? To realize this, this paper proposes a collaborative learning scheme for GNN-Transformer and constructs GTC architecture. GTC leverages the GNN and Transformer branch to encode node information from different views respectively, and establishes contrastive learning tasks based on the encoded cross-view information to realize self-supervised heterogeneous graph representation. For the Transformer branch, we propose Metapath-aware Hop2Token and CG-Hetphormer, which can cooperate with GNNs to attentively encode neighborhood information from different levels. As far as we know, this is the first attempt in the field of graph representation learning to utilize both GNNs and Transformer to collaboratively capture different view information and conduct cross-view contrastive learning. The experiments on real datasets show that GTC exhibits superior performance compared with state-of-the-art methods. Codes can be available at https://github.com/PHD-lanyu/GTC.

In-situ construction of integrated transition metals and metal oxides with carbon nanomaterial heterostructures to modulate electron redistribution for boosted water splitting

Heterostructure engineering has been proposed as a promising approach to construct high-efficiency bifunctional electrocatalyst for overall water splitting. Integrated transition metal and metal oxide heterointerfaces with carbon nanomaterials are designed to facilitate electrocatalytic performance toward overall water splitting. Fe/MnO heterostructures are fabricated on graphene using a one-step DC arc plasma technology. In this way, increased electrochemically active specific areas, accelerated charge transfer, and proper interfacial electronic structure can be achieved. Benefiting from the synergistic effect of multiple materials, fabricated Fe/MnO/graphene heterointerfaces can make the redistribution of electrons between heterointerfaces, which effectively optimizes adsorption/desorption energy of the reaction intermediates. Fe/MnO/graphene delivers excellent catalytic activity with only 362 mV and 339 mV overpotential to reach current density of 10 mA cm−2 for OER and HER and exceptional long-term stability in alkaline solution. As electrocatalyst at both the cathode and the anode of an alkaline electrolyzer simultaneously, Fe/MnO/graphene electrocatalyst requires a cell voltage of 1.987 V at a current density of 10 mA cm−2 for overall water splitting. Therefore, this work offers a feasible route to construct hierarchically nanohybrids as bifunctional electrocatalysts by combining transition metal and metal oxide with carbon nanomaterials.

Theoretical study on sequential splitting of droplets flowing through fractal tree-shaped microchannel networks

A theoretical model for describing the sequential splitting of droplets flowing through the fractal tree-shaped microchannel network with arbitrary branch level is developed to explore the mechanisms underlying the hydraulic imbalance on the high-throughput droplets production. Accordingly, detailed droplet splitting characteristics are presented, including the droplet velocities in branches, droplet distribution coefficient, and monodispersity of droplets production. It is found that the uniformity of droplet mainly depends on two key dimensionless parameters, namely Λ1 and Λ2, where Λ1 is determined by the initial working condition involving the initial lengths and viscosity of the continuous and discrete phases, the width of the 0th level channel, and the initial capillary number, and Λ2 is concerned with the outlet pressure pout, [2n-1] and the pressure drops of the continuous and discrete phases at the 0th level channel. The monodispersity of droplets goes down with the decreasing Λ1 and the increasing Λ2. Based on the Λ1 and Λ2, the optimal design strategies contributing to enhancing the droplet generation uniformity are recommended, including increasing Ca, enlarging the length of continuous phase flow at the main channel, and increasing the lengths of each level channels. Furthermore, the tree-shaped microchannel networks with higher branch level (n) have stronger ability to resist asymmetric disturbances. In particular, in our work, the width fractal dimension Δ = 2 is adopted as a proper key structure parameter, so as to ensure sequential breakup of droplet at each T-junction under symmetric condition.

Experimental and numerical investigation on oscillatory combustion characteristics of an integrated flameholder

Integrated flameholders are widely used in advanced afterburner. Oscillatory combustion can be easily caused by the complex flow field and non-uniform fuel distribution in advanced afterburner with integrated flameholders. Therefore, the oscillatory combustion characteristics under uniform and non-uniform fuel distribution downstream of integrated flameholder is investigated by using an experimental method with numerical simulation. The results show that oscillatory combustion is more likely to occur under the condition of non-uniform fuel distribution. When oscillatory combustion occurs, the main frequency is approximately 33.99 Hz and the flame variations can be divided into three phases: re-ignition phase, instability pre-transmission phase and extinction phase. Furthermore, three combustion states are observed at equivalence ratio Φ varied between 0.2 and 0.85: steady combustion, quasi-periodic oscillatory combustion and limit-cycle oscillatory combustion. Limit-cycle oscillatory combustion exhibits a relatively simple proper orthogonal decomposition structure and a longer axial motion wavelength than quasi-periodic oscillatory combustion. Notably, during oscillatory combustion, the pressure and heat release rate pulsations are roughly in the same frequency and phase, which shows that the oscillatory combustion is mainly caused by thermoacoustic interaction. These results provide guidance for further investigations of oscillatory combustion in advanced afterburner with integrated flameholders and development measures for its suppression.

Transformative approaches to managing student unrest in a South African university

Higher education and training institutions in South Africa have experienced widespread student unrest and crises in recent years, particularly within universities. This issue has been attributed to strained relationships between students and university management. Therefore, it is imperative to address the conflict gap between students and management in order to promote peaceful university operations. This study employed qualitative research, utilising decoloniality theory and a transformative paradigm lens within a qualitative research approach and participatory research design. Data was collected through focus group discussions (FGDs), with participants selected using a homogeneous sampling technique. For this study, three management employees, three students (SRC members), three lecturers, and three security officers from the chosen university were selected as participants using the homogeneous sampling technique. Data analysis was conducted using Braun and Clarke's six-step thematic analysis. One of the key findings is that the lack of a proper structure to manage unrest and the failure to involve students in decision-making pose significant challenges in the management of student unrest. The potential solutions to these challenges include the establishment of appropriate structures, the involvement of stakeholders in decision-making processes, and the development of common ground among stakeholders. These solutions could effectively address the issue at hand. Furthermore, a major recommendation is to engage society in order to address student unrest comprehensively. The study concludes that applying principles of openness and integrity is crucial in building and maintaining trust among stakeholders, as trust has been identified as a significant factor in bridging the gap between them.

The Use of Audio-Visual Media on Student Learning Interest in Explanatory Text Material

Background. The use of audio-visual media in education has gained increasing attention due to its potential to enhance student engagement and learning outcomes. In Indonesian language instruction, particularly in teaching explanatory text material, there is a need to explore innovative methods to improve student interest and comprehension. Purpose. This study aims to evaluate the impact of using audio-visual media on students' interest in learning explanatory text material in class VII-A SMP Negeri 2 Hiliduho. Method. A qualitative research method with a descriptive approach was employed. The study involved 20 students from class VII-A SMP Negeri 2 Hiliduho. Data were collected through observation, interviews, and documentation techniques. Results. The use of audio-visual media significantly increased students' interest and understanding of explanatory text material. Students demonstrated improved ability in determining appropriate terms and adjusting explanatory texts to their proper structure and characteristics. Audio-visual media, such as PowerPoint presentations and videos, made the material more engaging and comprehensible, facilitating a more efficient learning process. Students using audio-visual media showed higher levels of engagement compared to those who did not, as they were able to follow the learning flow more effectively. Conclusion. The findings suggest that audio-visual media play a crucial role in enhancing the learning experience for students studying explanatory text material. Teachers reported that these tools aided in more effective content delivery. The increased student engagement and improved understanding of the material highlight the potential of audio-visual media as a valuable instructional tool in Indonesian language education, particularly for explanatory text instruction.

Iron and ferritin deficiency in women with hypothyroidism and chronic lymphocytic thyroiditis - systematic review.

Iron is one of the essential microelements necessary for maintaining the body's homeostasis. It serves various roles, including being a crucial component in the proper structure of many enzymes and supporting the transport of oxygen and electrons. Its deficiency can lead to anaemia, which is a common clinical condition often associated with thyroid diseases. Iron deficiency is one of the most common nutritional deficiencies, and its prevalence is strongly associated with socioeconomic status. It is the primary cause of anaemia in 42% of children and 50% of women. Importantly, iron deficiency is placed among the top 5 causes of disability in women. Thyroid peroxidase (TPO) is an enzyme essential for the production of thyroid hormones, and iron is a key factor in its proper functioning. Therefore, in the case of iron deficiency, the activity of this enzyme is also reduced. Iron is also a factor that is important in epigenetic modification processes, and its deficiency may contribute to genomic changes potentially promoting the development of autoimmune thyroid diseases. Adequate supplementation in patients with Hashimoto's disease is one of the crucial elements of effective therapy. In addition to iodine, selenium, and magnesium supplementation, attention should be paid to proper iron intake. Iron is an element that is a component of the heme enzyme- thyroid peroxidase, which owes its activity to the binding of haem, and its function is the production of thyroid hormones. Iron can be delivered to the body in haem and non-haem forms. The haem form is found particularly in haemoglobin-rich red meat, but also in eggs, fish, and poultry. On the other hand, non-haem iron can be found in legumes, grains, fruits, and vegetables. Our study aimed to gather and summarise knowledge from scientific literature regarding iron deficiency anaemia and its association with hypothyroidism in women, as well as the possible mechanisms and pathogenesis of these conditions. The paper also aims to highlight that considering the high risk of iron deficiency, assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease.

Scyllatoxin-based peptide design for E. coli expression and HIV gp120 binding

Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the host cell's CD4. Previous inhibitors, including small molecules and CD4 mimetic peptides based on scyllatoxin, have demonstrated significant binding and neutralization capabilities but were often chemically synthesized or contained non-canonical amino acids. Microbial expression using natural amino acids offers advantages such as cost-effectiveness, scalability, and efficient production of fusion proteins. In this study, we enhanced the previous scyllatoxin-based synthetic peptide by substituting natural amino acids and successfully expressed it in E. coli. The peptide was optimized by mutating the C-terminal amidated valine to valine and glutamine, and by reducing the disulfide bonds from three to two. Circular dichroism confirmed proper secondary structure formation, and fluorescence polarization analysis revealed specific, concentration-dependent binding to HIV gp120, supported by molecular dynamics simulations. These findings indicate the potential for scalable microbial production of effective antiviral peptides, with significant applications in pharmaceutical development for HIV treatment.

Teachers’ Perspectives Towards Using STEAM Approach in English Classrooms

Objectives: The aim of this study is to see the perception of teachers towards STEAM approach in teaching students. The research asserts towards different views teachers have created for STEAM in educating students. This study highlights the awareness of STEAM pedagogy, and the challenges they may face during instructional implementation. Although, it is difficult to implement STEAM successfully, but it is a useful tool in teaching students' practical knowledge and skills. Methods: The present study is adopted using quantitative research method. The sample size selected from total population of teachers in Bahawalpur district were 50 in total. There were 25 males and 25 females who were selected through convenient sampling technique. Self-developed inventory was used as research tool to collect data from participants. Results: The findings of the study showed that the teachers are aware of using STEAM in classrooms and it greatly helps them to teach applied skills and knowledge. The results show that although teachers felt difficulty in evaluation and assisting students, they still feel that STEAM is a multi-disciplinary approach which is a great way to utilize full potential of students and makes teaching and learning exciting. Conclusions: The cumulative discussions that were found in the light of the study concluded that teachers wanted to implement STEAM in the classrooms, but they also wanted proper facilities and structure for applying this approach successfully as it requires training and resources.

Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.

The ability of cells to organize into tissues with proper structure and function requires the effective coordination of proliferation, migration, polarization, and differentiation across length scales. Skeletal muscle is innately anisotropic; however, few biomaterials can emulate mechanical anisotropy to determine its influence on tissue patterning without introducing confounding topography. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topography, C2C12 myoblasts collectively polarize in the stiffest direction. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of the same chemical formulation. These findings provide valuable insights for designing biomaterials that mimic anisotropic microenvironments and underscore the importance of stiffness anisotropy in orchestrating tissue morphogenesis.

Theoretical study on CO production mechanism from CO2 reduction on Cu–catalyst surface with different oxidation states

The rational design of copper (Cu)-based catalysts with different oxidation states is essential to achieve highly selective and efficient CO2 electroreduction. However, the effect of different oxide states of Cu-based catalysts has rarely been studied. Herein, the reaction mechanism of CO2 hydrogenation into CO on Cu-based catalysts with different oxidation states, such as Cu(111), Cu2O(111) and CuO(111), was studied using the density functional theory. The most favored pathway for CO production and the rate-controlling step on the three catalyst models were determined. The results show that, Cu2O (111) shows the best catalytic activity among the three catalysts due to the lowest activation barrier. The electronic structure analysis shows that Cu2O has the proper electronic structure to activate CO2 which is further reduced to CO. This work provides an important insight on the effect of oxidation state of Cu-based catalysts on the reduction of CO2 to CO.

Physiological aging and inflammation-induced cellular senescence may contribute to oligodendroglial dysfunction in MS

Aging affects all cell types in the CNS and plays an important role in CNS diseases. However, the underlying molecular mechanisms driving these age-associated changes and their contribution to diseases are only poorly understood. The white matter in the aging brain as well as in diseases, such as Multiple sclerosis is characterized by subtle abnormalities in myelin sheaths and paranodes, suggesting that oligodendrocytes, the myelin-maintaining cells of the CNS, lose the capacity to preserve a proper myelin structure and potentially function in age and certain diseases. Here, we made use of directly converted oligodendrocytes (dchiOL) from young, adult and old human donors to study age-associated changes. dchiOL from all three age groups differentiated in an comparable manner into O4 + immature oligodendrocytes, but the proportion of MBP + mature dchiOL decreased with increasing donor age. This was associated with an increased ROS production and upregulation of cellular senescence markers such as CDKN1A, CDKN2A in old dchiOL. Comparison of the transcriptomic profiles of dchiOL from adult and old donors revealed 1324 differentially regulated genes with limited overlap with transcriptomic profiles of the donors’ fibroblasts or published data sets from directly converted human neurons or primary rodent oligodendroglial lineage cells. Methylome analyses of dchiOL and human white matter tissue samples demonstrate that chronological and epigenetic age correlate in CNS white matter as well as in dchiOL and resulted in the identification of an age-specific epigenetic signature. Furthermore, we observed an accelerated epigenetic aging of the myelinated, normal appearing white matter of multiple sclerosis (MS) patients compared to healthy individuals. Impaired differentiation and upregulation of cellular senescence markers could be induced in young dchiOL in vitro using supernatants from pro-inflammatory microglia. In summary, our data suggest that physiological aging as well as inflammation-induced cellular senescence contribute to oligodendroglial pathology in inflammatory demyelinating diseases such as MS.