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Review

21 March 2025

Metabolic Regulation of T Cell Exhaustion

Cytotoxic CD8 T cells play a crucial role in controlling tumor progression. However, T cells infiltrating tumor tissues upregulate inhibitory receptors, reduce cytokine secretion, and lose their killing function, a state known as exhaustion. Thus, preventing or reversing T cell exhaustion is essential for sustaining a successful antitumor immune response. Recent studies have shown that T cell immunity not only requires the three primary signals—antigen receptor signaling, costimulation, and cytokines—but is largely shaped by endogenous and ambient metabolites as a fourth regulatory signal. Therefore, metabolic changes in the tumor microenvironment, caused by tumor cell proliferation and tissue remodeling, have a significant impact on the function of tumor-infiltrating T cells. This paper will review mechanisms by which three major types of metabolites—carbohydrates, lipids, and amino acids—influence T cell exhaustion in the tumor microenvironment, providing insights and directions for exploring metabolic targets in antitumor immunity.

Keywords: T cell exhaustion; Immunometabolism; Cancer immunology

Article

21 March 2025

Additive Manufacturing of Tungsten-Alloyed Tantalum from Polyhedral Shaped Powder Blends

Tantalum and tungsten are completely soluble in each other and are used in applications in the combined form of so-called tantaloys. They provide high melting points (Ta: 3017 °C, W: 3410 °C) and excellent corrosion resistance while maintaining high ductility for W contents up to 7.5 wt%. Providing good resistance to hydrogen embrittlement, Ta-W alloys are attractive candidates for applications in fusion reactors. This study demonstrated the feasibility of producing chemically homogeneous bulk material with fine grained microstructure from non-spherical powder blends with up to 7.5% tungsten using laser powder bed fusion (PBF-L/M). It is observed that cracking remains a challenge, especially with the increase in tungsten content. The effect of rapid solidification on the microhardness of up to 385 HV0.1 for 7.5% W is discussed. It provides initial indications of the possibility of achieving higher strengths and paves the way for further alloy development with regard to the additive manufacturing of this alloy family.

Keywords: Additive Manufacturing; Tantalum; Tantaloy; Refractory metals

Article

21 March 2025

Formation Mechanism and Structural Evolution of Mesophase Pitch via Phase Separation

Mesophase pitch is obtained through a two-stage treatment method combining stirring and non-stirring heat treatment of the catalytic cracking oil slurry. The structural evolution during the mesophase pitch forming process is analyzed using phase separation and testing by X-ray diffraction, Fourier Transform Infrared spectroscopy, and Thermogravimetric analysis. After a short period of non-stirring heat treatment, the solid-phase yield rapidly increases by 14.20 wt.%, reaching 46.70 wt.%. The softening point of the final mesophase pitch is all below 350 °C. The increase in yield and structural transformation are influenced by changes in the content of quinoline insoluble, as evidenced by the presence of C-H out-of-plane bending vibration at 670 cm−1. Based on the observed changes in composition and structure, this study proposes a hypothesis regarding the increase in mesophase pitch production during heat treatment.

Keywords: Mesophase pitch; Phase separation; Two-stage thermal polycondensation; FCC slurry

Opinion

21 March 2025

Classical MHC Class I Molecules as Modifiers of Brain Homeostasis and Neuroregeneration: Unraveling the Riddle?

As mankind breaks the boundaries of potential years to live, the process of aging imposes various cellular challenges, from less capacity of cell repair and damage to impaired protein formation, causing chronic low-level inflammation on tissues including the brain. Persistent chronic neuroinflammation can harm neurons, contributing to the development of neurodegeneration, a pathological process that affects cognitive function and is often reflected by dementia. This opinion article tries to recapitulate the influence that major histocompatibility class I (MHC-I) molecules have on brain homeostasis and how abnormalities in their expression can lead to cognitive deterioration. Studies carried out during recent years not only demonstrated that neurons and other central nervous system (CNS) cells express MHC-I molecules, but also that these molecules play essential roles in the establishment, function, and modeling of synapses in the CNS during the embryonic period, at birth and during adulthood, namely during inflammatory conditions. The accumulated body of evidence suggests that MHC-I molecules and the signaling pathways they regulate could provide clues on some of the molecular and cellular mechanisms regulating brain homeostasis and neuroregeneration in health and disease, thus becoming potential biomarkers of cognitive decline and targets for innovative immunotherapies.

Keywords: Aging; Alzheimer’s disease (AD); Central nervous system (CNS); Cognitive impairment; Cytoplasmic MHC-I tail; Dementia; MHC-I conformers; Parkinson’s disease (PD)

Article

20 March 2025

Fluctuations in Internal Water Footprint of Major Crops in Egypt: Implications for Sustainable Water Management

The scarcity of water represents a significant obstacle to the advancement of agriculture in Egypt, requiring the implementation of inventive water policies and effective resource management practices. The notion of virtual water, which considers the water contained within things, is a possible remedy to mitigate the strain on water resources. This study examines the changes over time in the amount of water used internally and the amount of virtual water exported by rice, maize, and wheat crops in Egypt between 2000 and 2018. The assessment evaluates the impact of climate variables, crop productivity, and renewable water sources on the internal water footprint. The study uses data from several sources and applies a Nonlinear Autoregressive Distributed Lag (NARDL) model to analyse how productivity, renewable water supplies, temperature, and precipitation affect the internal water footprint. The EVIEWS software is utilised for conducting statistical analysis. The results demonstrate that the internal water footprint and productivity of the crops studied vary over time, and climate conditions and the availability of water control this variation. The maximum internal water footprint values for rice, maize, and wheat were recorded in 2008, 2011, and 2017, respectively, aligning with the highest temperatures and available renewable water resources. The analysis reveals complex connections between the independent factors and the internal water footprint of each crop. Precipitation has an inverse correlation with the internal water footprint of rice, but renewable water resources have a favourable impact on the internal water footprint of wheat. The study emphasizes improving crop choices to minimize water usage and boost water output. Given Egypt’s expected water scarcity by 2025 and its reliance on Nile water for irrigation, implementing sustainable solutions for water resource management in agriculture is crucial. These findings give useful insights for policymakers and stakeholders in creating efficient water management policies and promoting food security in Egypt.

Keywords: Water scarcity; Virtual water; Internal water footprint; Crop productivity; Sustainable water management; Egypt

Review

20 March 2025

The Fate and Dynamics of Neural Stem Cells (NSCs) and Their Neurogenic Decline in Alzheimer’s Disease

Neural stem cells (NSCs) are crucial for neurogenesis in the mammalian brain, supporting the generation of neurons and glial cells during both development and adulthood. However, aging—driven by factors such as reduced growth factors, heightened inflammation, oxidative stress, and epigenetic modifications—leads to a decline in NSC activity, which is closely associated with cognitive decline. This article explores the significant reduction in neurogenesis observed in Alzheimer’s disease (AD), where amyloid-beta (Aβ) accumulation, tau pathology, mitochondrial dysfunction, and chronic neuroinflammation disrupt NSC function in the hippocampus and subventricular zone (SVZ). These disruptions impair NSC proliferation, differentiation, and migration, contributing to the progression of cognitive deficits. Additionally, this article examines experimental studies suggesting that deficits in neurogenesis often precede amyloid plaque formation in animal models, positioning impaired neurogenesis as a potential early biomarker for AD. Therapeutic strategies targeting neurogenesis, epigenetics, and inflammation—such as anti-inflammatory treatments, environmental enrichment, and modulation of systemic factors—hold promise for reversing neurogenic deficits and enhancing cognitive function. Furthermore, this article discusses both pharmacological agents and non-pharmacological strategies that show potential in promoting neurogenesis, though further research is needed to evaluate their safety and efficacy. The decline of NSC is driven by many interconnected factors, making it challenging to understand and address fully. This highlights the need for ongoing research.

Keywords: Alzheimer’s disease; Neural stem cells; Adult hippocampal neurogenesis; Subventricular zone (SVZ) neurogenesis; Amyloid-beta; Tau pathology; Neuroinflammation; Therapeutic strategies

Article

20 March 2025

Metabolic Engineering and Genome-Wide Adaptive Evolution for Efficient Reduction of Glycerol in Industrial Saccharomyces cerevisiae

The production of glycerol as a major by-product during yeast-based bioethanol fermentation arises directly from the need to re-oxidize excess NADH, which reduces conversion efficiency. In this study, an optimized Cas9-based genome editing method was performed to develop a mixotrophic CO2-fixing industrial Saccharomyces cerevisiae by heterologous expression of ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO form Pseudomonas sp.) and phosphoribulokinase (PRK form Spinach). Additionally, the gene encoding alcohol dehydrogenase (ADH2) responsible for converting ethanol to acetaldehyde was deleted, while the great wall-family protein kinase Rim15 gene was overexpressed to facilitate the reduction in glycerol content. The resulting CO2-fixing yeast M-2 led to a 21.5% reduction of the by-product glycerol in corn mash fermentation cultures at 39 ℃. Moreover, we established a novel gene mutators mediated genome-wide mutations system that accumulates distinct mutations in the industrial S. cerevisiae strains under the stress conditions to improve the robustness in the S. cerevisiae strains efficiently.

Keywords: Saccharomyces cerevisiae; Gene editing; Glycerol yield; Genome-wide mutation; Adaptive evolution; Robustness

Article

20 March 2025

Shared Decision Making for an Implantable Pulmonary Artery Monitoring Device in Heart Failure: A Pilot Study

Pulmonary artery (PA) pressure can be monitored remotely by a microelectromechanical sensor (MEMS) permanently implanted in the pulmonary artery. This device allows early management of fluid overload in heart failure so that diuresis can be initiated promptly, and hospitalization and other adverse events can be prevented. To test the methods and measures proposed to explore patient and provider perceptions of Shared Decision Making for the CardioMEMS pulmonary artery pressure monitoring device. A convenience sample of eight patient-provider dyads was enrolled at an ambulatory academic cardiology clinic and completed the shared decision making questionnaire in the clinic prior to the procedure. The majority of providers reported complete agreement that shared decision making occurred. Patients’ survey responses varied but remained positive. The survey used was feasible and effective. Dyad perceptions were positive and concordant in this small convenience sample. Future studies with larger samples are needed to develop interventions to promote behaviors necessary for shared decision making.

Keywords: CardioMEMS; Pulmonary artery pressure monitoring; Surgically implanted sensor; Heart failure; Shared decision making; Volume overload

Article

17 March 2025

A Strategy for Resisting the Vested Interests Driving the Collapse of the Biosphere and Civilisation

The biosphere and civilisation are facing existential and other major threats: climate change, biodiversity loss, nuclear war, social inequality/injustice, loss of human rights, and autocracy. These threats are driven by politically powerful vested interests supported by an economic system based on the exploitation of the environment and most people for the benefit of a wealthy minority. This article proposes a strategy to resist and weaken state capture, i.e., the influence of the vested interests driving the principal threats, while simultaneously facilitating the transition to a sustainable society. Despite the achievements of diverse community-based non-government organisations (CNGOs) campaigning on specific issues, scientists are now warning of the potential collapse of civilisation. As the threats are linked together in several ways, I propose a strategy to address them together to yield multiple benefits, supplementing campaigns on individual issues. A broad social movement—comprising an alliance between CNGOs devoted to the environment, social justice, human rights, and peace—could exert sufficient political power to expose and defeat the methods of state capture. Simultaneously, the movement could gain widespread community support by campaigning for a well-being economy, including universal basic services and a job guarantee, thus facilitating the transition to an ecologically sustainable, more socially just, and more peaceful civilisation.

Keywords: Collapse of civilisation; Vested interests; State capture; Sustainability; Neoliberalism; Political power; Social movement; Resistance

Article

17 March 2025

Experimental Study on A Novel Organic/Inorganic Green Deep Eutectic Solvents: Thermophysical Properties, Thermal Stability, and Utilization in Nanofluids

In response to the performance limitations of traditional heat transfer fluids under extreme conditions, a series of organic/inorganic deep eutectic solvents (DES), composed of ethylene glycol and different types of acetates, have been developed, and their downstream thermophysical properties, as well as their potential applications in nanofluids, have been explored. It is found that the prepared DESs significantly broaden the liquid phase temperature range, which ranges from −14~196 °C to −40~201 °C. The initial decomposition temperature increases from 85 °C to 130 °C, and the peak decomposition rate shifts from 175 °C to 206 °C. Subsequently, nanofluids were prepared by employing the selected ethylene glycol: potassium acetate-5:1 DES with carbon nanotube as nanofiller. The results reveal that the thermal conductivity of the nanofluid could be increased by approximately 3% compared to the base fluid, and the specific heat capacity was enhanced by 7.5% with a photothermal conversion efficiency reaching up to 42.7%. These results highlight the promising thermal stability and heat transfer properties of ethylene glycol-acetate DESs. Moreover, the nanofluids prepared from those DESs as base fluids provide useful references for the development of novel, green, and high-efficiency energy transportation fluids.

Keywords: Deep eutectic solvents; Thermophysical properties; Thermal stability; Nanofluid; Photothermal conversion efficiency
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