Topological effect of an intramolecular split G-quadruplex on thioflavin T binding and fluorescence light-up.

In this work, the topological effect on binding interaction between a G-quadruplex and thioflavin T (ThT) ligand was systematically investigated on a platform of an intramolecular split G-quadruplex (Intra-SG). Distinct fluorescence changes from ThT were presented in the presence of distinct split modes of Intra-SG structures and an intriguing phenomenon of target-induced fluorescence light-up occurred for split modes 2 : 10, 5 : 7 and 8 : 4. It was validated that hybridization between the Intra-SG spacer and target did not unfold the G-quadruplex, but facilitated the ThT binding. Moreover, the 3' guanine-rich fragment of Intra-SG was very susceptible to topology variation produced by the bound target strand. Additionally, a bioanalytical method was developed for ultrasensitive gene detection, confirming the utility of the ThT/Intra-SG complex as a universal signal transducer. It is believed that the results and disclosed rules will inspire researchers to develop many new DNA-based signal transducers in the future.

Dual-signal readout sensing of ATP content in single dental pulp stem cells during differentiation via functionalized glass nanopipettes.

Adenosine triphosphate (ATP) is regarded as the "energy currency" in living cells, so real-time quantification of content variation of intracellular ATP is highly desired for understanding some important physiological processes. Due to its single-molecule readout ability, nanopipette sensing has emerged as a powerful technique for molecular sensing. In this study, based on the effect of targeting-aptamer binding on ionic current, and fluorescence resonance energy transfer (FRET), we reported a dual-signal readout nanopipette sensing system for monitoring ATP content variation at the subcellular level. In the presence of ATP, the complementary DNA-modified gold nanoparticles (cDNAs-AuNPs) were released from the inner wall of the nanopipette, which leads to sensitive response variations in ionic current rectification and fluorescence intensity. The developed nanopipette sensor was capable of detecting ATP in single cells, and the fluctuation of ATP content in the differentiation of dental pulp stem cells (DPSCs) was further quantified with this method. The study provides a more reliable nanopipette sensing platform due to the introduction of fluorescence readout signals. Significantly, the study of energy fluctuation during cell differentiation from the perspective of energy metabolism is helpful for differentiation regulation and cell therapy.

Current Advances on the Single-Atom Nanozyme and Its Bioapplications.

Nanozymes, a class of nanomaterials mimicking the function of enzymes, have aroused much attention as the candidate in diverse fields with the arbitrarily tunable features owing to the diversity of crystalline nanostructures, composition, and surface configurations. However, the uncertainty of their active sites and the lower intrinsic deficiencies of nanomaterial-initiated catalysis compared with the natural enzymes promote the pursuing of alternatives by imitating the biological active centers. Single-atom nanozymes (SAzymes) maximize the atom utilization with the well-defined structure, providing an important bridge to investigate mechanism and the relationship between structure and catalytic activity. They have risen as the new burgeoning alternative to the natural enzyme from in vitro bioanalytical tool to in vivo therapy owing to the flexible atomic engineering structure. Here, focus is mainly on the three parts. First, a detailed overview of single-atom catalyst synthesis strategies including bottom-up and top-down approaches is given. Then, according to the structural feature of single-atom nanocatalysts, the influence factors such as central metal atom, coordination number, heteroatom doping, and the metal-support interaction are discussed and the representative biological applications (including antibacterial/antiviral performance, cancer therapy, and biosensing) are highlighted. In the end, the future perspective and challenge facing are demonstrated.

Rapid Synthesis of Trimetallic Nanozyme for Sustainable Cascaded Catalytic Therapy via Tumor Microenvironment Remodulation.

Tumor microenvironment (TME)-responsive nanozyme-catalyzed cancer therapy shows great potential due to its specificity and efficiency. However, breaking the self-adaption of tumors and improving the sustainable remodeling TME ability remains a major challenge for developing novel nanozymes. Here, a rapid method is developed first to synthesize unprecedented trimetalic nanozyme (AuMnCu, AMC) with a targeting peptide (AMCc), which exhibits excellent peroxidase-like, catalase-like, and glucose oxidase-like activities. The released Cu and Mn ions in TME consume endogenous H2 O2 and produce O2 , while the AMCccatalyzes glucose oxidation reaction to generate H2 O2 and gluconic acid, which achieves the starvation therapy by depleting the energy and enhances the chemodynamic therapy effect by lowering the pH of the TME and producing extra H2 O2 . Meanwhile, the reactive oxygen species damage is amplified, as AMCc can constantly oxidize intracellular reductive glutathione through the cyclic valence alternation of Cu and Mn ions, and the generated Cu+ elevate the production of ·OH from H2 O2 . Further studies depict that the well-designed AMCc exhibits the excellent photothermal performance and achieves TME-responsive sustainable starvation/photothermal-enhanced chemodynamic synergistic effects in vitro and in vivo. Overall, a promising approach is demonstrated here to design "all-in-one" nanozyme for theranostics by remodeling the TME.

NSC48160 targets AMPKα to ameliorate nonalcoholic steatohepatitis by inhibiting lipogenesis and mitochondrial oxidative stress.

Hepatic steatosis, which is triggered by dysregulation of lipid metabolism and redox equilibrium in the liver, is regarded as a risk factor in the non-alcoholic fatty liver disease (NAFLD). However, pharmacologic engagement of this process is difficult. We identified the small molecule NSC48160 as an effective agent against nonalcoholic steatohepatitis (NASH). We found that NSC48160 significantly lowered hepatic lipid levels in vitro and in vivo by activating the AMPKα-dependent pathway. AMPKα regulated its downstream pathway involved in lipogenesis (SREBP-1c/FASN pathway) and fatty acid oxidation (PPARα pathway). Metabonomics analysis combined with RNA-sequencing profiling revealed that NSC48160-induced lipogenesis is modulated by lipid metabolism. Moreover, NSC48160 dramatically reduces reactive oxygen species (ROS) production, restores the levels of the membrane potential and NAD+/NADH ratio, and improves mitochondrial respiration. These findings suggest that NSC48160 is a promising hit compound in the pursuit of a pharmacological approach in the treatment of NASH.

Boosting Photon Emission from the Chemiluminescence of Luminol Based on Host-Guest Recognition for the Determination of Dopamine.

Modulating the photon emission of the luminophore for boosting chemiluminescence (CL) response is very crucial for the construction of highly sensitive sensors via the introduction of functionalized materials. Herein, the integration of the emitter and coreactant accelerator into one entity is realized by simply assembling cucurbit[7]uril (CB[7]) on the surface of gold nanoparticles (AuNPs) through simple assembly via a Au-O bond. The loaded CB[7] on the AuNPs improves their catalytic capacity for the generation of hydroxyl radicals(•OH). Moreover, the host-guest recognition interaction between luminol and CB[7] enables the capture of luminol on AuNPs efficiently. Also, the intramolecular electron-transfer reaction between the luminol and •OH enables the CL response more effectively in the entity, which greatly boosts photon emission ca 100 folds compared with the individual luminol/H2O2. The host-guest recognition between luminol and CB[7] is revealed by Fourier transform infrared spectroscopy, electrochemical, and thermogravimetric characterization. Moreover, the proposed CL system is successfully used for the sensitive and selective determination of dopamine (DA) based on a synergistic quenching mechanism including the competition quenching and radical-scavenging effect from DA. The present amplified strategy by integrating recognized and amplified elements within one entity simplifies the sensing process and holds great potential for sensitive analysis based on the self-enhanced strategies.

CuFe Layered Double Hydroxide as Self-Cascade Nanoreactor for Efficient Antibacterial Therapy.

Nanozyme-induced reactive oxygen species (ROS)-dependent catalytic therapy has been developed into a powerful strategy against bacterial wound infections. However, the limited endogenous supply or instability of H2O2, the reliance on external stimuli for the generation of ROS, and the highly expressed glutathione (GSH) level make it a challenge to achieve high-performance therapeutic efficiency. In this work, a facile therapeutic strategy against bacterial infections with pristine CuFe layered double hydroxide (LDH) as the self-cascade nanoreactor is proposed without modification or additional energy input. CuFe LDH with an oxidase-like feature can catalyze the generation of multiple ROS, such as 1O2, ·O2-, and H2O2. And the self-generated H2O2 in the cascade nanoreactor could be further in situ transformed to ·OH owing to the peroxidase-like activity. As a result, the cell membrane of bacteria is destroyed, leading to death. Furthermore, its ultrahigh enzyme-like activity of CuFe LDH could effectively promote the breakdown of the biofilm structure. Additionally, the Cu2+-mediated GSH exhaustion of CuFe LDH further avoids the consumption of oxidized ROS and thereby significantly improves the sterilization effect. Finally, the as-prepared CuFe LDH with negligible side effects on normal tissues can be successfully used to eliminate the methicillin-resistant Staphylococcus aureus-infected wounds and accelerate their healing in the mouse model, which paves a new avenue as an antibacterial agent for clinical anti-infective treatment.

High CO2 adaptation mechanisms revealed in the miR156-regulated flowering time pathway.

Elevated CO2 concentrations have been observed to accelerate flowering time in Arabidopsis through the action of a highly conserved regulatory network controlled by miR156 and miR172. However, the network's robustness to the impact of increasing CO2 concentrations on flowering time remains poorly understood. In this study, we investigate this question by conducting a comprehensive analysis of the global landscape of network dynamics, including quantifying the probabilities associated with juvenile and flowering states and assessing the speed of the transition between them. Our findings reveal that a CO2 concentration range of 400-800ppm only mildly advances flowering time, contrasting with the dramatic changes from 200 to 300ppm. Notably, the feedback regulation of miR156 by squamosal promoter binding protein-like proteins (SPLs) plays a substantial role in mitigating the effects of increasing CO2 on flowering time. Intriguingly, we consistently observe a correlation between delayed flowering time and increased variance in flowering time, and vice versa, suggesting that this might be an intrinsic adaptation mechanism embedded within the network. To gain a deeper understanding of this network's dynamics, we identified the sensitive features within the feedback loops of miR156 SPLs and miR172-APETALA2 family proteins (AP2s), with the latter proving to be the most sensitive. Strikingly, our study underscores the indispensability of all feedback regulations in maintaining both juvenile and adult states as well as the transition time between them. Together, our research provides the first physical basis in plant species, aiding in the elucidation of novel regulatory mechanisms and the robustness of the miRNAs-regulated network in response to increasing CO2, therefore influencing the control of flowering time. Moreover, this study provides a promising strategy for engineering plant flowering time to enhance their adaptation and resilience.

Boosting Oxygen Reduction Reaction Kinetics by Designing Rich Vacancy Coupling Pentagons in the Defective Carbon.

In the energy conversion context, the design and synthesis of high-performance metal-free carbon nanomaterials with topological defects for the oxygen reduction reaction (ORR) are essential. Herein, we first report a template-assisted strategy to fabricate carbon defect electrocatalysts with rich vacancy coupling pentagons (VP) as active sites in two-dimensional (2D) carbon nanosheets (VP/CNs). Experimental characterizations verify the presence of abundant VP active sites in the VP/CNs electrocatalyst, and the ORR activity is linearly related to the amounts of VP active sites. In situ spectroscopic results identify that the VP/CNs can catalyze direct O-O bond cleavage, bypassing the formation of traditional *OOH intermediates, resulting in the fast kinetics of ORR via a dissociative pathway. The as-prepared VP/CNs show outstanding intrinsic activity for alkaline ORR (half-wave potential of 0.86 V vs reversible hydrogen electrode) with an almost 99% efficiency for four-electron selectivity, outperforming that using the benchmark of Pt/C. Density functional theory calculations further reveal that the cooperative effect between carbon vacancy and adjacent pentagons significantly increases the charge transfer and achieves a lower ORR reaction energy barrier compared with the counterpart of adjacent pentagons or single pentagon. The well-designed carbon defects pave a new avenue for the rational design of metal-free electrocatalysts with high efficiency.

Glass Nanopipette-Based Plasmonic SERS Platform for Single-Cell MicroRNA-21 Sensing during Apoptosis.

As one of the most widely distributed microRNAs, microRNA-21 (miRNA-21) significantly regulates target genes' expression levels and participates in many cellular and intercellular activities, and its abnormal expression is always related to some diseases, especially cancer. Hence, detecting miRNA-21, as a biomarker, at the single-cell level helps us to reveal cell heterogeneity and expression level variation during the state change of cells. In this study, we constructed a gold nanoparticles nanomembrane (AuNPs-NM)-modified plasmonic glass nanopipette (P-nanopipette) surface-enhanced Raman scattering (SERS) sensing platform to sensitively detect content variation of the intracellular miRNA-21 during the electrostimulus (ES)-induced apoptosis process. The cytoplasm-located miRNA-21 was first extracted by using the extraction DNA (HP1)-modified P-nanopipette through a hybridization chain reaction (HCR). The nanopipette was then incubated with a labeling DNA (HP2) and reporter 4-MBA-modified Raman tag. The Raman signal (collected from the tip area near the orifice within 1 µm) showed a good response to the content variation of intracellular miRNA-21 under ES, and the proposed single-cell SERS detection platform provides a simple way to study intracellular substance change and evaluate cancer treatment outcomes.

Global quantitative understanding of non-equilibrium cell fate decision-making in response to pheromone.

Cell-cycle arrest and polarized growth are commonly used to characterize the response of yeast to pheromone. However, the quantitative decision-making processes underlying time-dependent changes in cell fate remain unclear. In this study, we conducted single-cell level experiments to observe multidimensional responses, uncovering diverse fates of yeast cells. Multiple states are revealed, along with the kinetic switching rates and pathways among them, giving rise to a quantitative landscape of mating response. To quantify the experimentally observed cell fates, we developed a theoretical framework based on non-equilibrium landscape and flux theory. Additionally, we performed stochastic simulations of biochemical reactions to elucidate signal transduction and cell growth. Notably, our experimental findings have provided the first global quantitative evidence of the real-time synchronization between intracellular signaling, physiological growth, and morphological functions. These results validate the proposed underlying mechanism governing the emergence of multiple cell fate states. This study introduces an emerging mechanistic approach to understand non-equilibrium cell fate decision-making in response to pheromone.

Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

Effects of Mass Change on Liquid-Liquid Phase Separation of the RNA-Binding Protein Fused in Sarcoma.

In recent years, many experimental and theoretical studies of protein liquid-liquid phase separation (LLPS) have shown its important role in the processes of physiology and pathology. However, there is a lack of definite information on the regulation mechanism of LLPS in vital activities. Recently, we found that the intrinsically disordered proteins with the insertion/deletion of a non-interacting peptide segment or upon isotope replacement could form droplets, and the LLPS states are different from the proteins without those. We believed that there is an opportunity to decipher the LLPS mechanism with the mass change perspective. To investigate the effect of molecular mass on LLPS, we developed a coarse-grained model with different bead masses, including mass 1.0, mass 1.1, mass 1.2, mass 1.3, and mass 1.5 in atomic units or with the insertion of a non-interacting peptide (10 aa) and performed molecular dynamic simulations. Consequently, we found that the mass increase promotes the LLPS stability, which is based on decreasing the z motion rate and increasing the density and the inter-chain interaction of droplets. This insight into LLPS by mass change paves the way for the regulation and relevant diseases on LLPS.

Phytochemical gallic acid alleviates nonalcoholic fatty liver disease via AMPK-ACC-PPARa axis through dual regulation of lipid metabolism and mitochondrial function.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) usually includes NAFL called simple hepatosteatosis and nonalcoholic steatohepatitis (NASH) called more steatohepatitis. The latter is a leading pathogenic promotor of hepatocellular carcinoma (HCC). Phytochemical gallic acid (GA) has been proved to exert positive efficacy in HCC in our work, but it remains unclear whether its hepatoprotective effect attributes to the controlled transition from simple steatosis to steatohepatitis. PURPOSE: This work aims to provide mechanistic evidence that the therapeutic application of GA in NAFLD is indispensable for GA-meliorated NASH progression. METHODS: The high-fat diet (HFD)-fed mice and palmitic acid (PA) and oleic acid (OA)-treated hepatocytes were used collectively in this study. Bioinformatic analysis, clinical subjects, RNA-Seq, molecular docking, and confirmatory experiments were performed comprehensively to uncover the pathological link between the AMPK-ACC-PPARα axis and the treatment of NAFLD. RESULTS: By analyzing the clinical subjects and GEO database, we find a close link between the activation of AMPK-ACC-PPARα axis and the progression of NAFLD in human fatty liver. Subsequent assays show that GA exhibits pharmacological activation of AMPK, reprogramming lipid metabolism, and reversing mitochondrial function in cellular and murine fatty liver models. AMPK activation conferred substantial protection against murine NASH and fibrosis in the context of HFD-induced NAFLD. In contrast, silencing AMPK badly aggravates lipid deposition in hepatocytes, boosting NASH and NAFLD-associated HCC progression. The in silico docking, in vitro surface plasmon resonance and in vivo cellular thermal shift assay collectively reveal that GA directly interacts with AMPKα, which inactivates the ACC-PPARα axis signaling. Notably, GA repairs the liver damage, lipotoxicity, and mitochondrial respiratory capacity caused by excessive mtROS, while showing minimal effects in other major organs in mice. CONCLUSION: Our work identifies GA as an important suppressor of NAFLD-HCC progression, and underscores the AMPK-ACC-PPARα signal axis as a potential therapeutic target for NAFLD treatment.

Quantifying nonequilibrium dynamics and thermodynamics of cell fate decision making in yeast under pheromone induction.

Cellular responses to pheromone in yeast can range from gene expression to morphological and physiological changes. While signaling pathways are well studied, the cell fate decision-making during cellular polar growth is still unclear. Quantifying these cellular behaviors and revealing the underlying physical mechanism remain a significant challenge. Here, we employed a hidden Markov chain model to quantify the dynamics of cellular morphological systems based on our experimentally observed time series. The resulting statistics generated a stability landscape for state attractors. By quantifying rotational fluxes as the non-equilibrium driving force that tends to disrupt the current attractor state, the dynamical origin of non-equilibrium phase transition from four cell morphological fates to a single dominant fate was identified. We revealed that higher chemical voltage differences induced by a high dose of pheromone resulted in higher chemical currents, which will trigger a greater net input and, thus, more degrees of the detailed balance breaking. By quantifying the thermodynamic cost of maintaining morphological state stability, we demonstrated that the flux-related entropy production rate provides a thermodynamic origin for the phase transition in non-equilibrium morphologies. Furthermore, we confirmed that the time irreversibility in time series provides a practical way to predict the non-equilibrium phase transition.

Defective PtRuTe As Nanozyme with Selectively Enhanced Peroxidase-like Activity.

Noble metal based nanozymes show great potential in replacing natural enzymes; however, their development is greatly restricted by their relatively low specificity and activity. Herein, we report the synthesis of a class of amorphous/crystalline PtRuTe nanomaterials with a Pt/Te-enriched core and a Ru-enriched shell as efficient peroxidase mimics with selectively enhanced peroxidase-like activity and suppressed oxidase-like activity. We demonstrate that amorphous domains play a critical role in tuning and optimizing the catalytic properties. The PtRuTe nanozyme with high-percentage defects exhibits superior catalytic activities and kinetics, and the suppressed oxidase-like activity could diminish the interference of O2 in the glucose colorimetric assay. The high catalytic performance can be caused by amorphous phase induced electron redistribution and electronic interactions between different elements and the synergistic effect of multimetallic nanocrystals. The concurrent extraordinary peroxidase-like activity and suppressed oxidase-like activity guarantee the amorphous/crystalline PtRuTe nanozymes as promising alternatives of natural enzymes for biosensing and beyond.

Parallel DNA circuits by autocatalytic strand displacement and nanopore readout.

DNA nanotechnology provides a unique opportunity for molecular computation, with strand displacement reactions enabling controllable reorganization of nanostructures. Additional DNA strand exchange strategies with high selectivity for input will enable novel complex systems including biosensing applications. Herein, we propose an autocatalytic strand displacement (ACSD) circuit: initiated by DNA breathing and accelerated by a seesaw catalytic reaction, ACSD ensures that only the correct base sequence starts the catalytic cycle. Analogous to an electronic circuit with a variable resistor, two ACSD reactions with different rates are connected in parallel to mimic a parallel circuit containing branches with different resistances. Finally, we introduce a multiplexed nanopore sensing platform to report the output results of a parallel path selection system at the single-molecule level. By combining the ACSD strategy with fast and sensitive single-molecule nanopore readout, a new generation of DNA-based computing tools is established.

Unlocking the Low-Temperature Potential of Propylene Carbonate to -30 °C via N-Methylpyrrolidone.

As the one of the core electrolyte solvents for Li-ion batteries, ethylene carbonate (EC) is still irreplaceable for its balance of ionic conductivity and interfacial stability. However, it also defines the boundary for the low-temperature performance of the battery because of its high melting point (36.4 °C). Its immediate sibling, propylene carbonate (PC), has been proposed as its convenient substitute for its much lower melting point (-48.8 °C). Unfortunately, the propylene carbonate-graphite anode interfacial problem has been a puzzle since the days before the advent of the Li-ion battery. Among various strategies to mitigate this issue, blending in selected strong solvents for Li+ to bring down propylene carbonate's presence in the solvation shell has been proven often effective but the mechanism from the interfacial chemistry perspective remains unexplored. Herein, we study a new cosolvent, N-methylpyrrolidone (NMP), for PC-based electrolyte and observe excellent reversibility that approaches the commercial standard, far beyond the similar systems in the past. To understand the mechanism, solvation chemistry analysis and in situ characterizations are undertaken to probe the interfacial chemistry from various standpoints. Based on these results and further theoretical calculation, it is proposed that N-methylpyrrolidone has mediated the reduction process of propylene carbonate to facilitate the growth of a solid electrolyte interphase (SEI) layer akin to ethylene carbonate. Finally, an electrolyte has also been successfully developed based on the NMP/PC couple to outperform the commercial electrolyte by a clear margin when tested in a LiNi0.8Co0.1Mn0.1O2-graphite cell at -30 °C.

Lysine demethylase 1B (Kdm1b) enhances somatic reprogramming through inducing pluripotent gene expression and promoting cell proliferation.

Lysine demethylase 1B (Kdm1b) is known as an epigenetic modifier with demethylase activity against H3K4 and H3K9 histones and plays an important role in tumor progression and tumor stem cell enrichment. In this study, we attempted to elucidate the role of Kdm1b in somatic cell reprogramming. We found that exogenous expression of Kdm1b in human dermal fibroblasts (HDFs) can influence the epigenetic modifications of histones. Subsequent analysis further suggests that the overexpression of Kdm1b can promote cell proliferation, reprogram metabolism and inhibit cell apoptosis. In addition, a series of multipotent factors including Sox2 and Nanog, and several epigenetic factors that may reduce epigenetic barriers were upregulated to varying degrees. More importantly, HDFs transfected with the combination of Oct4 (POU5F1), Sox2, Klf4 and c-Myc and Kdm1b (OSKMK) achieved higher reprogramming efficiency. Therefore, we suggest that Kdm1b is an important epigenetic factor associated with pluripotency.

Facile Uniaxial Electrospinning Strategy To Embed CsPbBr3 Nanocrystals with Enhanced Water/Thermal Stabilities for Reversible Fluorescence Switches.

All-inorganic halide perovskite nanocrystals with their fascinating optical properties have drawn increasing attention as promising nanoemitters. However, due to the intrinsic poor colloidal stability against the external environment, the practical applications are greatly limited. Herein, a facile and effective strategy for the in situ encapsulation of CsPbBr3 NCs into highly dense multichannel polyacrylonitrile (PAN) nanofibers via a uniaxial electrospinning strategy is presented. Such a facile uniaxial electrospinning strategy enables the in situ formation of CsPbBr3 NCs in PAN nanofibers without the introduction of stabilizers. Significantly, the obtained CsPbBr3 nanofibers not only display intense fluorescence with a high quantum yield (≈48%) but also present high stability when exposed to water and air owing to the peripheral protecting matrix of PAN. After immersing CsPbBr3@PAN nanofiber films in water for 100 days, the quantum yield of CsPbBr3@PAN nanofibers maintained 87.5% of the original value, which was much higher than that using CsPbBr3 NCs. Furthermore, based on the spectral overlap between the electrochromic material of ruthenium purple and fluorescence of CsPbBr3@PAN nanofiber films with excellent water stability, a reversible fluorescence switch is constructed with good fatigue resistance, suggesting their promising applications.