Journals
2025 EN
Sittel Steven · Neuner Julian · Grenz Jonas M.
+3 more
Abstract The use of stable photosensitizers made on a multigram‐scale from cheap and available starting materials offers an extraordinary opportunity to translate small‐scale proof‐of‐concept photoreactions to widespread applications in non‐specialized laboratories, thereby promoting the implementation of light‐driven syntheses. Herein, we report an easy, multigram‐scale preparation of the exceptionally photo‐ and redoxstable chromium(III) complex [Cr(tpe) 2 ] 3+ (tpe=1,1,1‐tris(pyrid‐2‐yl)ethane) at room temperature. This photocatalyst was successfully employed in acetonitrile and in the “green” solvent water as demonstrated in visible‐light induced Schenck‐Ene reactions, Newman‐Kwart rearrangements, radical cation Diels‐Alder cycloadditions, oxidative decarboxylation and trifluoromethylation reactions with excellent substrate conversions and high turnover numbers. Gram‐scale photocatalytic reactions were conducted using a simple round‐bottom flask as reaction vessel and irradiation with energy‐efficient blue LEDs or even with sunlight. The stable photocatalyst was successfully recycled in up to 90–92% yields after the photoreactions.
Journals
2025 EN
Zhang Leisi · Zhang Honghai · Wang TingYu
+17 more
Abstract Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling‐focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression. Mechanistically, loss of COX4I1 induced mitochondrial stress and ferroptosis, disrupting mitochondrial ultrastructure and oxidative phosphorylation. CRISPR gene tiling scans, coupled with mitochondrial proteomics, dissected critical regions within COX4I1 essential for leukemia cell survival, providing detailed insights into the mitochondrial Complex IV assembly network. Furthermore, COX4I1 depletion or pharmacological inhibition of Complex IV (using chlorpromazine) synergized with venetoclax, providing a promising avenue for improved leukemia therapy. This study highlights COX4I1, a nuclear encoded mitochondrial protein, as a critical mitochondrial checkpoint, offering insights into its functional significance and potential clinical implications in AML.
Journals
2025 EN
Rouatbi Nadia · Walters Adam A. · Zam Alaa
+8 more
Abstract Immune checkpoint (ICP) blockade has shown limited effectiveness in glioblastoma (GBM), particularly in the mesenchymal subtype, where interactions between immune cells and glioblastoma cancer stem cells (GSCs) drive immunosuppression and therapy resistance. Tailoring ICPs specific to GSCs can enhance the antitumor immune response. This study proposes the use of lipid nanoparticles (LNPs) encapsulating CRISPR RNAs as an in vivo screening tool for ICPs in a syngeneic model of mesenchymal GSCs. Using PD‐L1 and CD47 to validate the proof of concept, intratumoral administration of LNPs in orthotopic tumors achieved efficient editing of ICPs, leading to enhanced immune cell infiltration within the tumor microenvironment. Targeting CD47 reduced tumor growth, suggesting improved cancer cell sensitization to the immune system post‐ICP editing. The study positions LNPs as a robust tool for in vivo validation of ICPs as therapeutic targets in clinically relevant GBM models. LNPs could serve as a screening tool in patient‐derived xenografts to identify and optimize ICP combinations, potentially expediting ICP translation and enhancing personalized GBM immunotherapies.
Journals
2025 EN
Wang Hui · Aiken Steven J · Wang Jian
Abstract Noise‐induced synaptopathy and relevant hidden hearing loss (NIS and NIHHL) have been a hot topic in hearing research for almost 15 years. The progress is summarized in this review to address the reversibility of the synaptic damage after the initial loss, and the role of functional deficit in the repaired synapses as the reason for hearing impairment in addition to the deafferentiation caused by the synaptic loss, per se. The evidence supporting the synaptic repair is summarized. It is pointed out that coding‐in‐noise deficit (CIND) may not be the major problem of NIS and NIHHL, since solid evidence supporting the existence of this deficit is not available even in animal studies, as well as in in human reports. Rather, temporal processing deficits are clearly demonstrated in subjects with NIS and potentially NIHHL. The idea of CIND as the major concern in NIHHL is proposed based upon the functional categorization of the auditory nerve (ANF) by spontaneous rate and the biased loss of the ribbon synapses innervation the low‐SR ANF. The limitation of this hypothesis is discussed in detail. The review also addresses the difficulty of translating animal data to humans and the need for new research in the future.
Journals
2025 EN
Steurer Matthias · Somers Paul · Kraft Kristian
+10 more
Abstract During light‐driven 3D additive manufacturing, an object represented in digital form is initially translated into a spatial distribution of light intensity (sequentially or in parallel), which then results in a spatial material distribution. To date, this process typically proceeds by photoexcitation of small functional molecules, leading to photochemically induced crosslinking of soft materials. Alternatively, thermal triggers can be employed, yet thermal processes are often slow and provide only low spatial localization. Nevertheless, sub‐micrometer ZnO structures for functional microelectronic devices have recently been laser‐printed. Herein, the photothermal laser‐printing of ZnO is advanced by i ) introducing single‐crystalline rather than amorphous sub‐micrometer ZnO shapes that crystallize in the hexagonal ZnO wurtzite structure, ii ) employing dimethyl sulfoxide (DMSO) instead of water, enabling higher local process temperatures without micro‐bubble formation, and iii ) using substrates tailored for light absorption and heat management, resolving the challenge of light to heat conversion. Finally, the herein‐demonstrated ZnO printing requires no post‐processing and is a cleanroom‐free technique for the fabrication of crystalline semiconductors.
Journals
2025 EN
Ni Duan · Tan Jian · Reyes Julen
+13 more
Abstract Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) believed to be driven by autoimmune mechanisms. Genetic and environmental factors are implicated in MS development, and among the latter, diets and nutrients are emerging as potential critical contributors. However, a comprehensive understanding of their impacts and the underlying mechanisms involved is lacking. Harnessing state‐of‐the‐art nutritional geometry analytical methods, it is first revealed that globally, increased carbohydrate supply is associated with increased MS disease burden, while fat supply has an opposite effect. Furthermore, in a MS mouse model, experimental autoimmune encephalomyelitis (EAE), it is found that an isocaloric diet high in carbohydrate aggravated EAE, while a diet enriched in fat (HF) is fully protective. This is reflected by reduced neuroinflammation and skewing toward anti‐inflammatory phenotypes. The protective effects from the HF diet are multifaceted. Metabolically, HF increased lipid storage in immune cells, correlating with their increased anti‐inflammatory IL‐10 production. Transcriptionally and epigenetically, HF feeding preprogrammed naïve T cells toward a less activated but more tolerogenic phenotype. It is showcased that manipulating diets is a potentially efficient and cost‐effective approach to prevent and/or ameliorate EAE. This exhibits translational potentials for prevention/intervention of MS and possibly other autoimmune diseases.
Journals
2025 EN
Anbalagan Aswin k. · Cummings Rebecca · Zhou Chenyu
+14 more
Abstract Despite constituting a smaller fraction of the qubit's electromagnetic mode, surfaces and interfaces can exert significant influence as sources of high‐loss tangents, which brings forward the need to reveal properties of these extended defects and identify routes to their control. Here, we examine the structure and composition of the metal‐substrate interfacial layer that exists in Ta/sapphire‐based superconducting films. Synchrotron‐based X‐ray reflectivity measurements of Ta films, commonly used in these qubits, reveal an unexplored interface layer at the metal‐substrate interface. Scanning transmission electron microscopy and core‐level electron energy loss spectroscopy identified an intermixing layer (≈0.65 ± 0.05 nm) at the metal‐substrate interface containing Al, O, and Ta atoms. Density functional theory modeling reveals that the structure and properties of the Ta/sapphire heterojunctions are determined by the oxygen content on the sapphire surface prior to Ta deposition for two atomic terminations of sapphire. Using a multimodal approach, we gained deeper insights into the interface layer between the metal and substrate, which suggests that the orientation of deposited Ta films depend on the surface termination of sapphire. The observed elemental intermixing at the metal‐substrate interface influences the thermodynamic stability and electronic behavior of the film, which may also affect qubit performance.
Journals
2025 EN
Li Xu · Jin Shuhan · Wang Danke
+8 more
Abstract Lipid metabolism disorders in both neurons and glial cells have been found in neurodegenerative (ND) patients and animal models. However, the pathological connection between lipid droplets and NDs remains poorly understood. The recent work has highlighted the utility of a neuron‐specific Arf1‐knockout mouse model and corresponding cells for elucidating the nexus between lipid metabolism disorders and amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, it is found that Arf1 deficiency first induced surplus fatty acid synthesis through the AKT‐mTORC1‐SREBP1‐FASN axis, which further triggered endoplasmic reticulum (ER)‐mitochondrial stress cascade via calcium flux. The organelle stress cascade further caused mitochondrial DNA (mtDNA) to be released into cytoplasm. Concurrently, the FASN‐driven fatty acid synthesis in the Arf1‐deficient neurons might also induce accumulation of sphingolipids in lysosomes that caused dysfunction of autophagy and lysosomes, which further promoted lysosomal stress and mitochondria‐derived extracellular vesicles (MDEVs) release. The released MDEVs carried mtDNA into microglia to activate the inflammatory pathways and neurodegeneration. The studies on neuronal lipid droplets (LDs) and recent studies of microglial LDs suggest a unified pathological function of LDs in NDs: activating the inflammatory pathways in microglia. This finding potentially provides new therapeutic strategies for NDs.
Journals
2025 UN
Nemani Srinivasa Kartik · Gilli Nicola · Goldy Steven
+9 more
Abstract MXenes are a family of two‐dimensional (2D) transition metal carbides, nitrides, and carbonitrides with potential applications in ceramics and composites due to their nanometer‐thick morphology, hydrophilic surfaces, and negative zeta potentials. In this study, we investigated titanium carbide MXene (Ti 3 C 2 T x ) as an additive in ultra‐high‐temperature ceramics (UHTCs), specifically zirconium diboride (ZrB 2 ). Homogeneous green bodies of Ti 3 C 2 T x and ZrB 2 were synthesized via electrostatic self‐assembly in aqueous media without surfactants and subsequently densified using field‐assisted (spark plasma) sintering. The incorporation of 0.5 wt.% MXene enhanced the relative density of ZrB 2 from ≈89% (pure ZrB 2 ) to ≈96% under identical sintering conditions. MXene addition significantly reduced the oxygen content from ≈5 at.% in pure ZrB₂ to ≈2–3 at.% at 2.5 wt.% MXene loading. The presence of MXene also facilitates the formation of a core–shell microstructure, where (Zr,Ti)B 2 shells encapsulate ZrB₂ cores, with arrays of dislocations observed at the core–shell interface. Mechanical characterizations show substantial improvements, including a 36% increase in hardness, a ≈12% enhancement in Young's modulus, and a ≈15% increase in flexural strength at 2.5 wt.% MXene loading. These findings demonstrate the potential of MXenes as effective sintering aids and reinforcement agents in UHTCs, offering promising pathways for advancing materials designed for extreme environments.
Journals
2025 EN
Decker Yann · Müller Andreas · Proulx Steven T.
Abstract Fluid and solute exchange between cerebrospinal fluid (CSF) spaces and the central nervous system (CNS) parenchyma are critical for maintaining neural homeostasis and clearing metabolites. Nevertheless, the pathways and mechanisms underlying fluid and solute exchange between these compartments remain poorly understood. Historically, solute exchange between CSF spaces and the CNS parenchyma has been attributed to diffusion primarily driven by concentration gradients. Recently, the glymphatic hypothesis has challenged this concept by proposing that fluid and solutes move through the brain parenchyma via bulk flow, with influx along arterial perivascular spaces (PVS) and efflux along venous PVS. In this study, we used dynamic contrast‐enhanced MRI to investigate the distribution of two different contrast agents of molecular weights <1 kDa and 17 kDa injected into the lateral ventricle under awake, low‐dose, and high‐dose anesthesia conditions. Our findings revealed an increased CSF bulk flow of both contrast agents from the lateral ventricles to the circle of Willis under awake and low‐dose anesthesia states. In contrast, solute movement into different regions of the brain parenchyma was size‐dependent and affected by the rate of clearance from the ventricles. These observations support the CSF sink hypothesis, emphasizing diffusion‐driven solute exchange as a key mechanism over glymphatic circulation.