Prodigiosin regulates cancer metabolism through interaction with GLUT1.

In contrast to normal cells, cancer cells predominantly utilise glycolysis for ATP generation under aerobic conditions, facilitating proliferation and metastasis. Targeting glycolysis is effective for cancer treatment. Prodigiosin (PDG) is a natural compound with various bioactivities, including anticancer effects. However, the precise action mechanisms and molecular targets of PDG, which has demonstrated efficacy in regulating glucose metabolism in cancer cells, remain elusive. Here, we aimed to investigate the anti-cancer activity of PDG and mechanism in cancer metabolism. PDG regulated cancer metabolism by suppressing intracellular ATP production rate and levels. It inhibited glycolysis and mitochondrial oxidative phosphorylation, impeding ATP production dependent on both glycolysis and mitochondrial respiration. Moreover, it inhibited cellular glucose uptake by directly interacting with glucose transporter 1 without affecting its mRNA or protein levels in HCT116 cells. We provide insights into the anti-cancer effects of PDG mediated via cancer metabolism regulation, suggesting its therapeutic potential for cancer.

Neto proteins differentially modulate the gating properties of Drosophila NMJ glutamate receptors.

The formation of functional synapses requires co-assembly of ion channels with their accessory proteins which controls where, when, and how neurotransmitter receptors function. The auxiliary protein Neto modulates the function of kainate-type glutamate receptors in vertebrates as well as at the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse widely used for genetic studies on synapse development. We previously reported that Neto is essential for the synaptic recruitment and function of glutamate receptors. Here, using outside-out patch-clamp recordings and fast ligand application, we examine for the first time the biophysical properties of recombinant Drosophila NMJ receptors expressed in HEK293T cells and compare them with native receptor complexes of genetically controlled composition. The two Neto isoforms, Neto-α and Neto-ß, differentially modulate the gating properties of NMJ receptors. Surprisingly, we found that deactivation is extremely fast and that the decay of synaptic currents resembles the rate of iGluR desensitization. The functional analyses of recombinant iGluRs that we report here should greatly facilitate the interpretation of compound in vivo phenotypes of mutant animals.

Sustainable 3D printing by reversible salting-out effects with aqueous salt solutions.

Achieving a simple yet sustainable printing technique with minimal instruments and energy remains challenging. Here, a facile and sustainable 3D printing technique is developed by utilizing a reversible salting-out effect. The salting-out effect induced by aqueous salt solutions lowers the phase transition temperature of poly(N-isopropylacrylamide) (PNIPAM) solutions to below 10 °C. It enables the spontaneous and instant formation of physical crosslinks within PNIPAM chains at room temperature, thus allowing the PNIPAM solution to solidify upon contact with a salt solution. The PNIPAM solutions are extrudable through needles and can immediately solidify by salt ions, preserving printed structures, without rheological modifiers, chemical crosslinkers, and additional post-processing steps/equipment. The reversible physical crosslinking and de-crosslinking of the polymer through the salting-out effect demonstrate the recyclability of the polymeric ink. This printing approach extends to various PNIPAM-based composite solutions incorporating functional materials or other polymers, which offers great potential for developing water-soluble disposable electronic circuits, carriers for delivering small materials, and smart actuators.

Highly Stable Heating Fibers of Ti3C2Tx MXene and Polyacrylonitrile via Synergistic Thermal Annealing.

Nanohybrid assemblies provide an effective platform for integrating the intrinsic properties of individual components into microscale fibers. In this study, a novel approach for creating mechanically and environmentally stable MXene fibers through the synergistic assembly of MXene and polyacrylonitrile (PAN), is introduced. Unlike fibers generated via a conventional stabilization process, which relies on air-based stabilization to transform the PAN molecules into ring structures fundamental to carbon fibers, the hybrid fibers are annealed in an Ar atmosphere. This unique approach suggests MXene can serve as an oxygen provider that is essential for stabilizing PAN. As a result, significantly improved interfiber compactness is achieved and the oxidation stability of MXene is enhanced under atmospheric conditions. The resulting fibers exhibit exceptional stability, even after extended exposure to high humidity and elevated temperatures. This highlights the suitability of the thermally annealed MXene-PAN (T-MX-PAN) fibers as robust electric heating elements. Notably, these fibers consistently generate heat over 1800 bending cycles. When integrated into fabrics, they demonstrate the capability to generate sufficient heat for melting ice and rapid evaporation. This study highlights the potential of T-MX-PAN fibers as next-generation wearable heaters and offers valuable insights into advancing wearable technology in demanding environments.

Stilbenoid derivatives as potent inhibitors of HIF-1α-centric cancer metabolism under hypoxia.

Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor associated with cancer metabolism and is regarded as a potent anticancer therapeutic strategy within the hypoxic microenvironment of cancer. In this study, stilbenoid derivatives were designed, synthesized, and assessed for their capacity to inhibit HIF-1α-associated cancer metabolism and evaluated for inhibition of cancer cell viability and HIF activation. Through the structure-activity relationship studies, compound 28e was identified as the most potent derivative. Specifically, under the hypoxic condition, 28e reduced the accumulation of HIF-1α protein and the expression of its target genes related to glucose metabolism without affecting the expression of HIF-1α mRNA. Furthermore, 28e inhibited glucose uptake, glycolytic metabolism, and mitochondrial respiration, decreasing cellular ATP production under hypoxic conditions. In addition, 28e displayed significant anti-tumor effects and effectively suppressed the accumulation of HIF-1α protein in tumor tissue in vivo xenograft model. These findings suggest that our stilbenoid derivatives exert their anticancer effects by targeting HIF-1α-centered cancer metabolism under hypoxic conditions.

Structural Asymmetry and Chiral-Induced Spin Selectivity in Chiral Palladium-Halide Semiconductors.

Chiral Pb-free metal-halide semiconductors (MHSs) have attracted considerable attention in the field of spintronics due to various interesting spin-related properties and chiral-induced spin selectivity (CISS) effect. Despite their excellent chemical and structural tunability, the material scope and crystal structure of Pb-free chiral MHSs exhibiting the CISS effect are still limited; chiral MHSs that have metal-halide structures of octahedra and tetrahedra are only reported. Here, we report a new class of chiral MHSs, of which palladium (Pd)-halides are formed in 1D square-pyramidal structures or 0D square-planar structures, with a general formula of ((R/S-MBA)2PdBr4)1-x((R/S-MBA)2PdCl4)x (MBA = methylbenzylammonium; x = 0, 0.25, 0.5, 0.75, and 1) for the first time. The crystals adopt the 1D helical chain of Pd-halide square-pyramid (for x = 0, 0.25, 0.5, and 0.75) and 0D structure of Pd-halide square-plane (for x = 1). All the Pd-halides are distorted by the interaction between the halide and the chiral organic ammonium and arranged in a noncentrosymmetric position. Circular dichroism (CD) for ((R/S-MBA)2PdBr4)1-x((R/S-MBA)2PdCl4)x indicates that chirality was transferred from chiral organic ammonium to Pd-halide inorganics. ((R-MBA)2PdBr4)1-x((R-MBA)2PdCl4)x (x = 0, 0.25, 0.5, and 0.75) shows a distortion index of 0.127-0.128, which is the highest value among the previously reported chiral MHSs to the best of our knowledge. We also find that (R/S-MBA)2Pd(Br1-xClx)4 crystals grow along the out-of-plane direction during spin coating and have high c-axis orientation and crystallinity, and (R/S-MBA)2Pd(Br1-xClx)4 (x = 0 and 0.5) crystals exhibit a CISS effect in polycrystalline bulk films. These results demonstrate the possibility of a new metal-halide series with square-planar structures or square-pyramidal structures for future spintronic applications.

scRNA-seq data from the larval Drosophila ventral cord provides a resource for studying motor systems function and development.

The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated by anatomical identification, to create a comprehensive census of larval VNC cell types. We show that the neural lineages that comprise the adult VNC are already defined, but quiescent, at the larval stage. Using fluorescence-activated cell sorting (FACS)-enriched populations, we separate all motor neuron bundles and link individual neuron clusters to morphologically characterized known subtypes. We discovered a glutamate receptor subunit required for basal neurotransmission and homeostasis at the larval neuromuscular junction. We describe larval glia and endorse the general view that glia perform consistent activities throughout development. This census represents an extensive resource and a powerful platform for future discoveries of cellular and molecular mechanisms in repair, regeneration, plasticity, homeostasis, and behavioral coordination.

CYB5R3 functions as a tumor suppressor by inducing ER stress-mediated apoptosis in lung cancer cells via the PERK-ATF4 and IRE1α-JNK pathways.

Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD+) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD+ activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer.

Programming Anisotropic Functionality of 3D Microdenticles by Staggered-Overlapped and Multilayered Microarchitectures.

Natural sharkskin features staggered-overlapped and multilayered architectures of riblet-textured anisotropic microdenticles, exhibiting drag reduction and providing a flexible yet strong armor. However, the artificial fabrication of three-dimensional (3D) sharkskin with these unique functionalities and mechanical integrity is a challenge using conventional techniques. In this study, it is reported on the facile microfabrication of multilayered 3D sharkskin through the magnetic actuation of polymeric composites and subsequent chemical shape fixation by casting thin polymeric films. The fabricated hydrophobic sharkskin, with geometric symmetry breaking, achieves anisotropic drag reduction in frontal and backward flow directions against the riblet-textured microdenticles. For mechanical integrity, hard-on-soft multilayered mechanical properties are realized by coating the polymeric sharkskin with thin layers of zinc oxide and platinum, which have higher hardness and recovery behaviors than the polymer. This multilayered hard-on-soft sharkskin exhibits friction anisotropy, mechanical robustness, and structural recovery. Furthermore, coating the MXene nanosheets provides the fabricated sharkskin with a low electrical resistance of ≈5.3 Ω, which leads to high Joule heating (≈229.9 °C at 2.75 V). The proposed magnetomechanical actuation-assisted microfabrication strategy is expected to facilitate the development of devices requiring multifunctional microtextures.

Surface nitrided MXene sheets with outstanding electroconductivity and oxidation stability.

Two-dimensional Ti3C2Tx MXenes are promising candidates for a wide range of film- or fiber-based devices owing to their solution processability, high electrical conductivity, and versatile surface chemistry. The surface terminal groups (Tx) of MXenes can be removed to increase their inherent electrical performance and ensure chemical stability. Therefore, understanding the chemical evolution during the removal of the terminal groups is crucial for guiding the production, processing, and application of MXenes. Herein, we investigate the effect of chemical modification on the electron-transfer behavior during the removal of the terminal groups by annealing Ti3C2Tx MXene single sheets under argon (Ar-MXene) and ammonia gas (NH3-MXene) conditions. Annealing in ammonia gas results in surface nitridation of MXenes and preserves the electron-abundant Ti3C2 structure, whereas annealing MXene single sheets in Ar gas results in the oxidation of the titanium layers. The surface-nitrided MXene film exhibits an electrical conductivity two times higher than that of the Ar-MXene film. The oxidation stability is quantified by calculating the oxidation rate constants for severe reactions with H2O2. The surface-nitrided MXene is 13 times more stable than Ar-MXene. The investigation of MXene single sheets provides fundamental insights that are valuable for designing electrically conductive and chemically stable MXenes.

FSP1 confers ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma in NRF2-dependent and -independent manner.

Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.

Impermeable Graphene Skin Increases the Heating Efficiency and Stability of an MXene Heating Element.

A Joule heater made of emerging 2D nanosheets, i.e., MXene, has the advantage of low-voltage operation with stable heat generation owing to its highly conductive and uniformly layered structure. However, the self-heated MXene sheets easily get oxidized in warm and moist environments, which limits their intrinsic heating efficiencies. Herein, an ultrathin graphene skin is introduced as a surface-regulative coating on MXene to enhance its oxidative stability and Joule heating efficiency. The skin layer is deposited on MXene using a scalable solution-phased layer-by-layer assembly process without deteriorating the excellent electrical conductivity of the MXene. The graphene skin comprises narrow and hydrophobic channels, which results in ≈70 times higher water impermeability of the hybrid film of graphene and MXene (GMX) than that of the pristine MXene. A complementary electrochemical analysis confirms that the graphene skin facilitates longer-lasting protection than conventional polymer coatings owing to its tortuous pathways. In addition, the sp2 planar carbon surface with a low heat loss coefficient improves the heating efficiency of the GMX, indicating that this strategy is promising for developing adaptive heating materials with a tractable voltage range and high Joule heating efficiency.

Investigating the interfacial properties of halide perovskite/TiOx heterostructures for versatile photocatalytic reactions under sunlight.

Heterostructures of metal halide perovskites and TiOx are efficient photocatalytic materials owing to the combination of the advantages of each compound, specifically the high absorption coefficients and long charge-carrier lifetimes of perovskites, and efficient photocatalytic activity of TiOx. However, chemical reduction of CO2 using PNC/TiOx heterostructures without organic solvents has not been reported yet. Here, we report the first solvent-free reduction of CO2 using amorphous TiOx with embedded colloidal perovskite nanocrystals (PNCs). The combination was obtained by carrying out hydrolysis of titanium butoxide (TBOT) on the PNC surface without high-temperature calcination. We proposed a mechanism involving photoexcited electrons being transferred from PNCs to TBOT, enabling photocatalytic reactions using TiOx under visible-light excitation. We demonstrated efficient visible-light-driven photocatalytic reactions at PNC/TiOx interfaces, specifically with a CO production rate of 30.43 µmol g-1 h-1 and accelerated degradation of organic pollutants under natural sunlight. Our work has provided a simple path toward both efficient CO2 reduction and photocatalytic degradation of organic dyes.

Hemicyanine-Based Near-Infrared Fluorescence Off-On Probes for Imaging Intracellular and In Vivo Nitroreductase Activity.

Nitroreductase (NTR) has the ability to activate nitro group-containing prodrugs and decompose explosives; thus, the evaluation of NTR activity is specifically important in pharmaceutical and environmental areas. Numerous studies have verified effective fluorescent methods to detect and image NTR activity; however, near-infrared (NIR) fluorescence probes for biological applications are lacking. Thus, in this study, we synthesized novel NIR probes (NIR-HCy-NO2 1-3) by introducing a nitro group to the hemicyanine skeleton to obtain fluorescence images of NTR activity. Additionally, this study was also designed to propose a different water solubility and investigate the catalytic efficiency of NTR. NIR-HCy-NO2 inherently exhibited a low fluorescence background due to the interference of intramolecular charge transfer (ICT) by the nitro group. The conversion from the nitro to amine group by NTR induced a change in the absorbance spectra and lead to the intense enhancement of the fluorescence spectra. When assessing the catalytic efficiency and the limit of detection (LOD), including NTR activity imaging, it was demonstrated that NIR-HCy-NO2 1 was superior to the other two probes. Moreover, we found that NIR-HCy-NO2 1 reacted with type I mitochondrial NTR in live cell imaging. Conclusively, NIR-HCy-NO2 demonstrated a great potential for application in various NTR-related fields, including NTR activity for cell imaging in vivo.

Grafting Behavior of Amine Ligands for Surface Modification of MXene.

Surface modification to improve the oxidation stability and dispersibility of MXene in diverse organic media is a facile strategy for broadening its application. Among the various ligands that can be grafted on the MXene surface, oleylamine (OAm), with amine functionalities, is an advantageous candidate owing to its strong interactions and commercial viability. OAms are grafted onto MXene through covalent bonds induced by nucleophilic reactions and H bonds in liquid interface reactions at room temperature. In addition, this grafting behavior of the ligand was characterized by a reduction in the slope with an increase in the ligand concentration (Cl), confirming that the OAms were grafted via Langmuir-like behavior, and the monolayer of OAms was developed via two distinct steps (I: lying-down phase; II: ordered monolayer). MXene nanosheets modified by OAm (OAm-MX) are highly dispersible in a wide range of organic solvents owing to the alkyl chain of the OAms, which induces hydrophobic properties on the surface of MXene. The OAm-MX dispersion exhibits outstanding oxidation and dispersion stability and remarkable coating performance on a wide range of substrates owing to their excellent solution processability. Therefore, this study provides fundamental insights into the adsorption behavior and interaction between amine ligands and MXene nanosheets for the surface chemistry of MXene.

Advances in Solution-Processed OLEDs and their Prospects for Use in Displays.

This review outlines problems and progress in development of solution-processed organic light-emitting diodes (SOLEDs) in industry and academia. Solution processing has several advantages such as low consumption of materials, low-cost processing, and large-area manufacturing. However, use of a solution process entails complications, such as the need for solvent resistivity and solution-processable materials, and yields SOLEDs that have limited luminous efficiency, severe roll-off characteristics, and short lifetime compared to OLEDs fabricated using thermal evaporation. These demerits impede production of practical SOLED displays. This review outlines the industrial demands for commercial SOLEDs and the current status of SOLED development in industries and academia, and presents research guidelines for the development of SOLEDs that have high efficiency, long lifetime, and good processability to achieve commercialization.

Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

Cancer-specific cytotoxicity of pyridinium-based ionic liquids by regulating hypoxia-inducible factor-1α-centric cancer metabolism.

Owing to their unique properties and biological activities, ionic liquids (ILs) have attracted research interest in pharmaceutics and medicine. Hypoxia-inducible factor (HIF)- 1α is an attractive cancer drug target involved in cancer malignancy in the hypoxic tumor microenvironment. Herein, we report the inhibitory activity of ILs on the HIF-1α pathway and their mechanism of action. Substitution of a dimethylamino group on pyridinium reduced hypoxia-induced HIF-1α activation. It selectively inhibited the viability of the human colon cancer cell line HCT116, compared to that of the normal fibroblast cell line WI-38. These activities were enhanced by increasing the alkyl chain length in the pyridinium. Under hypoxic conditions, dimethylaminopyridinium reduced the accumulation of HIF-1α and its target genes without affecting the HIF1A mRNA level in cancer cells. It suppressed the oxygen consumption rate and ATP production by directly inhibiting electron transfer chain complex I, which led to enhanced intracellular oxygen content and oxygen-dependent degradation of HIF-1α under hypoxia. These results indicate that dimethylaminopyridinium suppresses the mitochondria and HIF-1α-dependent glucose metabolic pathway in hypoxic cancer cells. This study provides insights into the anticancer activity of pyridinium-based ILs through the regulation of cancer metabolism, making them promising candidates for cancer treatment.

Effect of Chemical Agents on the Morphology and Chemical Structures of Microplastics.

Increased demand for plastics leads to a large amount of plastic manufacturing, which is accompanied by inappropriate disposal of plastics. The by-products of these waste plastics are microplastics (MPs; less than 5 nm in size), which are produced because of various environmental and physicochemical factors, posing hazardous effects to the ecosystem, such as the death of marine organisms due to the swallowing of plastic specks of no nutritional value. Therefore, the collection, preparation, identification, and recycling of these microsized plastics have become imperative. The pretreatment of MPs requires numerous chemical agents comprising strong acids, bases, and oxidizing agents. However, there is limited research on the chemical resistance of various MPs to these substances to date. In this study, the chemical resistance of five species of MPs (high-density polyethylene, low-density polyethylene, polystyrene, polyethylene terephthalate, and polypropylene) to sulfuric acid, hydrochloric acid, hydrogen peroxide, potassium hydroxide, and sodium hydroxide was studied. The MPs were reacted with these chemical reagents at preset temperatures and durations, and variations in morphology and chemical structures were detected when the MPs were reacted with mineral acids, such as sulfuric acid. The data pertaining to these changes in MP properties could be a significant reference for future studies on MP pretreatment with strong acids, bases, and oxidizing agents.

Sub-Second Joule-Heated RuO2-Decorated Nitrogen- and Sulfur-Doped Graphene Fibers for Flexible Fiber-type Supercapacitors.

Graphene-based fiber-shaped supercapacitors (FSSCs) have received considerable attention as potential wearable energy storage devices owing to their simple operating mechanism, flexibility, and long-term stability. To date, energy storage capacities of supercapacitors have been significantly improved via strategies such as heteroatom doping and the incorporation of pseudocapacitive metal oxides. Herein, we develop a novel and scalable direct-hybridization method that combines heteroatom doping and metal oxide hybridization for the fabrication of high-performance FSSCs. Using porous and highly conductive nitrogen and sulfur co-doped graphene fibers (NS-GFs) as self-heating units, we successfully convert ruthenium hydroxide anchored to the surface into ruthenium oxide nanoparticles after programmed sub-second electrothermal annealing without structural damage of the fibers. The resulting fibers show an increased gravimetric capacitance of 68.88 F g-1 compared to that of the pristine NS-GF (8.32 F g-1), excellent cyclic stability maintaining 96.67% of the initial capacitance after 20 000 continuous charging/discharging cycles, and good mechanical flexibility. The findings of this work advocate a successful Joule heating strategy for preparing high-performance graphene-based metal oxide hybrid FSSCs for use in energy storage applications.