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Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.
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Ataxina-3 , Doença de Machado-Joseph , Trealose , Trealose/farmacologia , Humanos , Ataxina-3/metabolismo , Ataxina-3/genética , Doença de Machado-Joseph/metabolismo , Doença de Machado-Joseph/tratamento farmacológico , Células HEK293 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Agregados Proteicos/efeitos dos fármacos , Mutação , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Agregação Patológica de Proteínas/metabolismo , PeptídeosRESUMO
Hydrogel-based interfacial solar-driven evaporation (ISDE) gives full play to the highly adjustable physical and chemical properties of hydrogel, which endows ISDE systems with excellent evaporation performance, anti-pollution properties, and mechanical behavior, making it more promising for applications in seawater desalination and wastewater treatment. This review systematically introduces the latest advances in hydrogel-based ISDE systems from three aspects: the required properties, the preparation methods, and the role played in application scenarios of hydrogels used in ISDE. Additionally, we also discuss the remaining challenges and potential opportunities in hydrogel-based ISDE systems. By summarizing the latest research progress, we hope that researchers in related fields have some insight into the unique advantages of hydrogels in the ISDE field and contribute our efforts so that ISDE technology reaches the finishing line of practical application on the hydrogel track.
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In colloid quantum dot light-emitting diodes (QLEDs), the control of interface states between ZnO and quantum dots (QDs) plays a vital role. We present a straightforward and efficient method using a negative corona discharge to modify the QD film, creating a dipole moment at the interface of QDs and magnesium-doped ZnO (ZnMgO) for balanced charge carrier distribution within the QDs. This process boosts external quantum efficiencies in red, green, and blue QLEDs to 17.71%, 14.53%, and 9.04% respectively. Notably, optimized devices exhibit significant enhancements, especially at lower brightness levels (1000 to 10,000â cd·m-2), vital for applications in mobile displays, TV screens, and indoor lighting.
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To achieve net-zero emissions by 2050, we need economic means of sequestering carbon dioxide (CO2) and reducing greenhouse gas emissions (GHG). We analyze the sequestration potential of the Intermountain West (I-West) region, US, as a primary energy transition hub through analysis of wellbore retrofit potential and emission reduction in both fugitive gas abatement and flare gas. We selected the I-West region due to its abundant energy sources and oil and gas production legacy. Preliminary analysis hints that well retrofits can breathe new life into a well at a fraction of the cost of a new drill. With millions of potential candidates in the US, even a modest fraction (1% or less) suitable for retrofit could accelerate the shift to large-scale CO2 sequestration. Fugitive gas, the unintentional release of wellbore gases such as methane, is a significant emissions source. Through conservative analysis, it is estimated that wellhead leakage alone may account for 5 million tonnes of carbon dioxide equivalent (CO2e) emissions. We conclude by assessing the CO2 emissions from flaring, which is the burning of associated gas during well operations, conservative analysis indicates flaring contributes another 2 million tonnes of CO2 emissions to the region. We find that with targeted retrofit and better controls on emissions sources, the I-West region can make a significant impact in the nation's push to become net-zero. This study outlines economic feasibility and actionable items to achieve the critical reductions in emissions and increases in sequestration necessary to attain net zero.
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Dióxido de Carbono , Gases de Efeito Estufa , Dióxido de Carbono/análise , Estados Unidos , Gases de Efeito Estufa/análise , Efeito EstufaRESUMO
Piezochromic materials refer to a class of matters that alter their photoluminescence (PL) colors in response to the external stimuli, which exhibit promising smart applications in anti-counterfeiting, optoelectronic memory and pressure-sensing. However, so far, most reported piezochromic materials have been confined to organic materials or hybrid materials containing organic moieties with limited piezochromic range of less than 100â nm in visible region. Here, we achieved an intriguing piezochromism in all-inorganic zero-dimensional (0D) Cs3Cu2Cl5 nanocrystals (NCs) with a considerable piezochromic range of 232â nm because of their unique inorganic rigid structure. The PL energy shifted from the lowest-energy red fluorescence (1.85â eV) to the highest-energy blue fluorescence (2.83â eV), covering almost the entire visible wavelength range. Pressure-modulated self-trapped exciton emission between different energy levels of self-trapped states within Cs3Cu2Cl5 NCs was the main reason for this piezochromism property. Note that the quenched emission, which is over five times more intense than that in the initial state, is retained under ambient conditions upon decompression. This work provides a promising pressure indicating material, particularly used in pressure stability monitoring for equipment working at extreme environments.
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BACKGROUND: Apatinib, a novel tyrosine kinase inhibitor independently developed by China, has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) in recent years. For more than a decade, sorafenib has been the classic first-line treatment option for patients with advanced HCC. However, the results of clinical studies comparing the efficacy and safety of these 2 drugs are still controversial. Therefore, the aim of this meta-analysis is to evaluate the efficacy and safety of apatinib versus sorafenib as first-line treatment for advanced HCC. METHODS: Up to August 14, 2023, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang were searched, and clinical studies of experimental group (apatinib or apatinib plus transarterial chemoembolization [TACE]) versus control group (sorafenib or sorafenib plus TACE) in the first-line treatment of advanced HCC were included. Two researchers evaluated the quality of the included studies and extracted the data. Revman 5.4 software was used for meta-analysis. RESULTS: A total of 12 studies involving 1150 patients were included. Five studies are apatinib alone versus sorafenib alone, and the other 7 studies are apatinib plus TACE versus sorafenib plus TACE. The results of the meta-analysis showed that compared with sorafenib alone, apatinib could improve (ORâ =â 3.06, 95%CI: 1.76-5.31), had no advantage in improving DCR (ORâ =â 1.52, 95%CI: 0.86-2.68) and prolonging PFS (HRâ =â 1.35, 95%CI: 0.94-1.96), and was significantly worse in prolonging OS (HRâ =â 1.43, 95%CI: 1.08-1.88). Similarly, apatinib plus TACE was inferior to sorafenib plus TACE in prolonging OS (HRâ =â 1.15, 95%CI: 1.03-1.28), although it improved ORR (ORâ =â 1.49, 95%CI: 1.03-2.16). In terms of adverse drug events, the overall incidence of adverse events, and the incidence of drug reduction and discontinuation in the experimental group were significantly higher than those in the control group (Pâ <â .05). The incidence of hypertension, proteinuria, and oral mucositis in the experimental group was significantly higher than that in the control group (Pâ <â .05). CONCLUSION: In the setting of first-line treatment of advanced HCC, apatinib has improved short-term efficacy (ORR) compared with sorafenib, but the safety and long-term efficacy of apatinib are inferior to sorafenib.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/patologia , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêuticoRESUMO
Overproduction of reactive oxygen species by damaged mitochondria after ischemia is a key factor in the subsequent cascade of damage. Delivery of therapeutic agents to the mitochondria of damaged neurons in the brain is a potentially promising targeted therapeutic strategy for the treatment of ischemic stroke. In this study, we developed a ceria nanoenzymes synergistic drug-carrying nanosystem targeting mitochondria to address multiple factors of ischemic stroke. Each component of this nanosystem works individually as well as synergistically, resulting in a comprehensive therapy. Alleviation of oxidative stress and modulation of the mitochondrial microenvironment into a favorable state for ischemic tolerance are combined to restore the ischemic microenvironment by bridging mitochondrial and multiple injuries. This work also revealed the detailed mechanisms by which the proposed nanodelivery system protects the brain, which represents a paradigm shift in ischemic stroke treatment.
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BACKGROUND: To investigate the impact of radiotherapy (RT) on recurrence and survival in patients with locally advanced upper rectal cancer underwent curative resection. METHODS: 363 locally advanced upper rectal cancer cases were identified from the database of our hospital from 2010 to 2018. All patients underwent curative resection and had the lower margin of the tumor located 10-15 cm from the anal verge, among them, 69 patients received pre- or post-operative radiotherapy and 294 patients without. Local control and survivals were compared, and stratification grouping based on European Society for Medical Oncology risk factors were further compared. 1:2 propensity score matching analysis was used to reduce the impact of confounding factors. RESULTS: There were 207 patients after 1:2 matching (RT group:non-RT group = 69:138). The 5-year overall survival (OS) of the RT group and non-RT group after matching was 84.1% and 80.9%, respectively(P = 0.440); the 5-year local recurrence-free survival (LRFS) was 96.5% and 94.7%, respectively(P = 0.364); the 5-year distant metastasis-free survival (DMFS) was 76.8% and 76.9%, respectively(P = 0.531). Subgroup analysis showed that radiotherapy could not significantly improve the overall survival, local recurrence, and distant metastasis with or without poor prognostic features. In the high-risk subgroup, the 5-year OS was 76.9% and 79.6% for patients treated with radiotherapy and without (P = 0.798), LRFS was 94.8% and 94.2%, respectively (P = 0.605), DMFS 68.7% and 74.7%, respectively (P = 0.233). CONCLUSIONS: Our results suggest that radiotherapy could not improve local control and survival for locally advanced upper rectal cancer patients underwent curative resection, even in the cases with poor prognostic features.
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Neoplasias Retais , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Prognóstico , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/patologiaRESUMO
The strained interface of core@shell nanocrystals (NCs) can effectively modulate the energy level alignment, thereby significantly affecting the optical properties. Herein, the unique photoluminescence (PL) response of doped Mn ions is introduced as a robust probe to detect the targeted pressure-strain relation of CdS@ZnS NCs. Results show that the core experiences actually less pressure than the applied external pressure, attributed to the pressure-induced optimized interface that reduces the compressive strain on core. The pressure difference between core and shell increases the conduction band and valence band offsets and further achieves the core@shell configuration transition from quasi type II to type I. Accordingly, the PL intensity of CdS@ZnS NCs slightly increases, along with a faster blue-shift rate of PL peak under low pressure. This study elucidates the interplay between external physical pressure and interfacial chemical stress for core@shell NCs, leading to precise construction of interface engineering for practical applications.
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Near-infrared (NIR) quantum dot (QD) light-emitting diodes (LEDs) (NIR-QLEDs) for recognition and tracking applications underpin the future of night-vision technology. However, the performance of environmentally benign materials and devices has lagged far behind that of their Pb-containing counterparts. In this study, we demonstrate the superior performance of NIR-QLEDs based on efficient AgAuSe QDs with contact interface mediation. Consequently, we reveal that using cysteamine-treated QD film contact heterointerfaces can effectively eliminate contact defects in devices and preserve their excellent emissive properties. Additionally, the dipole moment orientation of the coordinated additives is inverse of the heterojunction potential difference, simultaneously blocking electrons and enhancing hole injection in operando, optimizing the LED charge injection balance. These devices exhibit a high external quantum efficiency (EQE) and a power conversion efficiency (PCE) of 15.8 and 12.7% at 1046 nm, respectively, a sub-band gap turn-on voltage of 0.9 V, and a low current density (over 10% of the EQE from 0.0017 to 0.31 mA cm-2). These are the highest EQE and PCE values ever reported for environmentally benign NIR-QLEDs. The results of this study can provide a general strategy for the practical application of QDs in electroluminescent devices.
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In this study, a highly promising bacterium was isolated from sandstone oil in the Ordos Basin, named strain NS-6 which exhibited exceptional urease production ability and demonstrated superior efficiency in inducing the deposition of calcium carbonate (CaCO3). Through morphological and physiochemical characteristics analysis, as well as 16S rRNA sequencing, strain NS-6 was identified as Neobacillus mesonae. The activity of urease and the formation of CaCO3 increased over time, reaching a maximum of 7.9 mmol/L/min and 184 mg (4.60 mg/mL) respectively at 32 h of incubation. Scanning Electron Microscopy (SEM) revealed CaCO3 crystals ranging in size from 5 to 6 µm, and Energy Dispersive X-ray (EDX) analysis verified the presence of calcium, carbon, and oxygen within the crystals. X-ray Diffraction (XRD) analysis further confirmed the composition of these CaCO3 crystals as calcite and vaterite. Furthermore, the maximum deposition of CaCO3 by strain NS-6 was achieved using response surface methodology (RSM), amounting to 193.8 mg (4.845 mg/mL) when the concentration of calcium ions was 0.5 mmol/L supplemented with 0.9 mmol/L of urea at pH 8.0. Genome-wide analysis revealed that strain NS-6 possesses a chromosome of 5,736,360 base pairs, containing 5,442 predicted genes, including 3,966 predicted functional genes and 1,476 functionally unknown genes. Genes like ureA, ureB, and ureC related to urea catabolism were identified by gene annotation, indicating that strain NS-6 is a typical urease-producing bacterium and possesses a serial of genes involved in metabolic pathways that mediated the deposition of CaCO3 at genetic level.
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Currently, mainstream lanthanide probes with fluorescence located in the second near-infrared subwindow of 1500-1700 nm (NIR-IIb) are predominantly Er(III)-based nanoparticles (NPs). Here we report a newly developed NIR-IIb fluorescent nanoprobe, α-Tm NP (cubic-phase NaYF4@NaYF4:Tm@NaYF4), with an emission at 1630 nm. We activate the 1630 nm emission of Tm(III) in α-Tm NP through the large spread of the Stark split sublevels induced by the crystal-field effect of the α-NaYF4 host. Further, we systematically investigated the effect of crystalline structure of the host NaYF4 NP (cubic phase (α) or hexagonal phase (ß)), the type and concentrations of dopants (Yb(III), Tm(III), and Ca(II) ions) in the α-phase host, and the thicknesses of the interlayer and inert shell on the NIR-IIb fluorescence of Tm(III). The ultimate nanostructure presents a significant enhancement factor of the NIR-IIb photoluminescence intensity of Tm(III) up to â¼315. With this bright NIR-IIb fluorescent nanoprobe, we demonstrate high-spatial-resolution time-coursing imaging of breast cancer bone metastasis.
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Liquid desiccant technology is an energy-efficient substitute for technologies that are conventionally applied for temperature and humidity control; however, innovative desiccant solutions have not been extensively explored in terms of their performance and feasibility. This work aimed to investigate desiccant solutions with moisture sorption analysis technically and economically. Various conditions of temperature and humidity were tested in a climatic chamber and the moisture absorption and desorption capacity, thermo-chemical energy storage capacity, and cost of conventional and innovative desiccant solutions were assessed by experiment. Calcium chloride showed the highest moisture desorption capacity (0.3113 gH2O/gsol in the climatic chamber at 50 °C and 25% RH) and the lowest cost, despite its low moisture absorption capacity. Ionic liquids show high moisture absorption capacity (as high as 0.429 gH2O/gsol in the climatic chamber at 25 °C and 90% RH) and could be used as additives (in which a maximum increase of 84.1% was observed for moisture absorption capacity due to the addition of ionic liquids), and thus, they are promising substitutes for conventional desiccant solutions. As solutions for better performance under various conditions were identified, the study will advance liquid desiccant technology.
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Nowadays, the soar of photovoltaic performance of perovskite solar cells has set off a fever in the study of metal halide perovskite materials. The excellent optoelectronic properties and defect tolerance feature allow metal halide perovskite to be employed in a wide variety of applications. This article provides a holistic review over the current progress and future prospects of metal halide perovskite materials in representative promising applications, including traditional optoelectronic devices (solar cells, light-emitting diodes, photodetectors, lasers), and cutting-edge technologies in terms of neuromorphic devices (artificial synapses and memristors) and pressure-induced emission. This review highlights the fundamentals, the current progress and the remaining challenges for each application, aiming to provide a comprehensive overview of the development status and a navigation of future research for metal halide perovskite materials and devices.
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Aluminum gallium nitride (AlGaN) is a nanohybrid semiconductor material with a wide bandgap, high electron mobility, and high thermal stability for various applications including high-power electronics and deep ultraviolet light-emitting diodes. The quality of thin films greatly affects their performance in applications in electronics and optoelectronics, whereas optimizing the growth conditions for high quality is a great challenge. Herein, we have investigated the process parameters for the growth of AlGaN thin films via molecular dynamics simulations. The effects of annealing temperature, the heating and cooling rate, the number of annealing rounds, and high temperature relaxation on the quality of AlGaN thin films have been examined for two annealing modes: constant temperature annealing and laser thermal annealing. Our results reveal that for the mode of constant temperature annealing, the optimum annealing temperature is much higher than the growth temperature in annealing at the picosecond time scale. The lower heating and cooling rates and multiple-round annealing contribute to the increase in the crystallization of the films. For the mode of laser thermal annealing, similar effects have been observed, except that the bonding process is earlier than the potential energy reduction. The optimum AlGaN thin film is achieved at a thermal annealing temperature of 4600 K and six rounds of annealing. Our atomistic investigation provides atomistic insights and fundamental understanding of the annealing process, which could be beneficial for the growth of AlGaN thin films and their broad applications.
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The mitochondrial calcium uniporter is a Ca2+ channel that imports cytoplasmic Ca2+ into the mitochondrial matrix to regulate cell bioenergetics, intracellular Ca2+ signaling, and apoptosis. The uniporter contains the pore-forming MCU subunit, an auxiliary EMRE protein, and the regulatory MICU1/MICU2 subunits. Structural and biochemical studies have suggested that MICU1 gates MCU by blocking/unblocking the pore. However, mitoplast patch-clamp experiments argue that MICU1 does not block, but instead potentiates MCU via allosteric mechanisms. Here, we address this direct clash of the proposed MICU1 function. Supporting the MICU1-occlusion mechanism, patch-clamp demonstrates that purified MICU1 strongly suppresses MCU Ca2+ currents, and this inhibition is abolished by mutating the MCU-interacting K126 residue. Moreover, a membrane-depolarization assay shows that MICU1 prevents MCU-mediated Na+ flux into intact mitochondria under Ca2+-free conditions. Examining the observations underlying the potentiation model, we found that MICU1 occlusion was not detected in mitoplasts not because MICU1 cannot block, but because MICU1 dissociates from the uniporter complex. Furthermore, MICU1 depletion reduces uniporter transport not because MICU1 can potentiate MCU, but because EMRE is down-regulated. These results firmly establish the molecular mechanisms underlying the physiologically crucial process of uniporter regulation by MICU1.
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Cálcio , Proteínas de Transporte da Membrana Mitocondrial , Cálcio/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Canais de Cálcio/metabolismo , Membranas Mitocondriais/metabolismo , Cálcio da Dieta , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismoRESUMO
The design of optimal infrastructure is essential for the deployment of commercial and large-scale carbon capture and storage (CCS) technology. During the design process, it is important to consider CO2 capture and storage locations and CO2 transportation pipelines to minimize the total project cost. SimCCS, first introduced in 2009, is an integrated open-source tool to optimize CCS infrastructure. The core CCS infrastructure design problem in SimCCS is structured as a mixed-integer linear programming problem by selecting the optimal pipeline routes, searching CO2 source capture and storage locations, and determining the corresponding CO2 amounts to meet desired capture targets. Multiple important and practical features have been developed to the latest version of SimCCS, SimCCS3.0. One of these features is phase-based modeling which enables users to dynamically design the CCS infrastructure. We demonstrate the phased-based modeling capability using two CCS infrastructure optimization case studies. The results from these case studies reveal that the phase-based modeling capability in SimCCS is particularly useful to optimize the dynamic deployment of CCS projects.
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BACKGROUND: Sex determination occurs across animal species, but most of our knowledge about its mechanisms comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. RESULTS: In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used it to demonstrate that this species has an XX/XY sex determination system. We demonstrate that the X and Y chromosomes have pseudoautosomal and non-recombining regions. We then use the linkage map and a method based on the depth of sequencing coverage to identify genes encoded in the non-recombining region and show that many of them have male gonad-specific expression. In addition, we demonstrate that recombination rates are enhanced in the female genome and that the haploid chromosome number in Hydractinia is n = 15. CONCLUSIONS: These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination and the evolution of sex chromosomes.
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Hidrozoários , Cromossomos Sexuais , Masculino , Feminino , Animais , Cromossomos Sexuais/genética , Mapeamento Cromossômico , Cromossomo Y/genética , Hidrozoários/genética , Evolução MolecularRESUMO
Copper(I)-based halides have recently attracted increasing attention as a substitute for lead halides, owing to their nontoxicity, abundance, unique structure, and optoelectric properties. However, exploring an effective strategy to further improve their optical activities and revealing structure-optical property relationships still remain a great concern. Here, by using high pressure technique, a remarkable enhancement of self-trapped exciton (STE) emission associated with the energy exchange between multiple self-trapped states in zero-dimensional lead-free halide Cs3 Cu2 I5 NCs is successfully achieved. Furthermore, high-pressure processing endows the piezochromism of Cs3 Cu2 I5 NCs by experiencing a white light and a strong purple light emission, which is able to be stabilized at near-ambient pressure. The distortion of [Cu2 I5 ] clusters composing of tetrahedral [CuI4 ] and trigonal planar [CuI3 ] and the decreased Cu-Cu distance between the adjacent Cu-I tetrahedron and triangle are responsible for the significant STEs emission enhancement under high pressure. The experiments combined with first-principles calculations not only shed light on the structure-optical property relationships of [Cu2 I5 ] clusters halide, but also provide guidance for improving emission intensity that is highly desirable in solid-state lighting applications.