USP14 modulates cell pyroptosis and ameliorates doxorubicin-induced cardiotoxicity by deubiquitinating and stabilizing SIRT3.

This study investigates the role of the deubiquitinating enzyme USP14 in alleviating doxorubicin (DOX)-induced cardiotoxicity (DIC), particularly concerning its mechanism of regulating pyroptosis through the stabilization of the mitochondrial protein SIRT3. Using in vivo and in vitro models, the research demonstrated that USP14 overexpression protects against DOX-induced cardiac damage by modulating pyroptosis. Silencing SIRT3 via siRNA revealed that SIRT3 is a key intermediary molecule in USP14-mediated regulation of pyroptosis. Notably, DOX exposure resulted in decreased USP14 expression, while its overexpression preserved mitochondrial function and reduced oxidative stress by stabilizing SIRT3. Immunoprecipitation confirmed that USP14 stabilizes SIRT3 through deubiquitination. These findings position USP14 as a promising therapeutic target for mitigating DOX-induced cardiotoxicity by stabilizing SIRT3 and maintaining mitochondrial integrity, suggesting potential novel strategies for cardio-protection in chemotherapy.

Expanding the Toolbox of Oxidants: Controllable Etching of Ultrasmall Au Nanoparticles toward Tailorable NIR-II Luminescence and Ligand-Mediated Biodistribution and Clearance.

Oxidant-driven and controllable etching of small-sized nanoparticles (NPs, d < 3 nm) and tailorable modulation of their optical properties are challenging due to the high reactivity and complicated surface chemistry. Herein, we present a facile strategy for highly controllable oxidative etching of ultrasmall AuNPs and tailorable modulation of luminescence. The proper choice of a moderate oxidant, ClO-, could not only selectively etch the Au(I)-thiolate motifs from the nanoparticle surface at the subnanometer scale but also retained a stable metallic core structure without aggregation, which impressively prompted the wide-range luminescent switching from the visible to second near-infrared (NIR-II) region. The resultant oxidized AuNPs displayed highly luminescent NIR-II emission with a quantum yield of 3.0%, excellent monodispersed stability, ideal biocompatibility, and tunable shielding effects against protein adsorption. With those outstanding features, oxidized AuNPs could be utilized as nanoprobes for long-lasting and in vivo bioimaging of associated metabolic behaviors with distinguishable organ-specific targeting capabilities and ligand-mediated kinetics in nanoparticle clearance. These findings expand the toolbox of oxidants for the controllable synthesis of NIR-II nanoprobes and open up a path for exploring diverse ligand interactions on ultrasmall AuNPs with organs or tissues that might advance their monitoring applications for a wide range of clinically important diseases.

Effects of season and water quality on community structure of planktonic eukaryotes in the Chaohu Lake Basin.

Introduction: Analyzing the correlation between planktonic eukaryotic communities (PECs) and aquatic physicochemical parameters (APPs) provides important references for predicting the impact of climate change and human activities on aquatic ecosystems. Methods: To assess the influence of seasons and APPs on PEC structures in lakes and rivers, we utilized high-throughput sequencing of the 18S rRNA gene to analyze PEC structures in a lake and seven rivers in the Chaohu Lake Basin and analyzed their correlations with APPs. Results: Our results revealed that PEC structure was significantly affected by season, with the highest α-diversity observed in summer. Furthermore, we identified several APPs, including water temperature, conductivity, dissolved oxygen, pH, phosphate, total phosphorus, trophic level index (TLI), nitrate, ammonia nitrogen, and total nitrogen, that significantly influenced PEC structures. Specifically, we found that Stephanodiscus hantzschii, Simocephalus serrulatus, Cryptomonas sp. CCAC_0109, Pedospumella encystans, Actinochloris sphaerica, Chlamydomonas angulosa, Gonyostomum semen, Skeletonema potamos, Chlamydomonas klinobasis, Pedospumella sp., and Neochlorosarcina negevensis were significantly correlated to TLI, while Limnoithona tetraspina, Theileria sp., and Pseudophyllomitus vesiculosus were significantly correlated to the water quality index (WQI). However, our random forest regression analysis using the top 100 species was unable to accurately predict the WQI and TLI. Discussion: These results provide valuable data for evaluating the impact of APPs on PEC and for protecting water resource in the Chaohu Lake Basin.

Memory-Augmented 3D Point Cloud Semantic Segmentation Network for Intelligent Mining Shovels.

The semantic segmentation of the 3D operating environment represents the key to intelligent mining shovels' autonomous digging and loading operation. However, the complexity of the operating environment of intelligent mining shovels presents challenges, including the variety of scene targets and the uneven number of samples. This results in low accuracy of 3D semantic segmentation and reduces the autonomous operation accuracy of the intelligent mine shovels. To solve these issues, this paper proposes a 3D point cloud semantic segmentation network based on memory enhancement and lightweight attention mechanisms. This model addresses the challenges of an uneven number of sampled scene targets, insufficient extraction of key features to reduce the semantic segmentation accuracy, and an insufficient lightweight level of the model to reduce deployment capability. Firstly, we investigate the memory enhancement learning mechanism, establishing a memory module for key semantic features of the targets. Furthermore, we address the issue of forgetting non-dominant target point cloud features caused by the unbalanced number of samples and enhance the semantic segmentation accuracy. Subsequently, the channel attention mechanism is studied. An attention module based on the statistical characteristics of the channel is established. The adequacy of the expression of the key features is improved by adjusting the weights of the features. This is done in order to improve the accuracy of semantic segmentation further. Finally, the lightweight mechanism is studied by adopting the deep separable convolution instead of conventional convolution to reduce the number of model parameters. Experiments demonstrate that the proposed method can improve the accuracy of semantic segmentation in the 3D scene and reduce the model's complexity. Semantic segmentation accuracy is improved by 7.15% on average compared with the experimental control methods, which contributes to the improvement of autonomous operation accuracy and safety of intelligent mining shovels.

Prediction of Geometric Dimensions of Deposited Layer Produced Using Laser-Arc Hybrid Additive Manufacturing.

Laser-arc hybrid additive manufacturing (LAHAM) holds substantial potential in industrial applications, yet ensuring dimensional accuracy remains a major challenge. Accurate prediction and effective control of the geometrical dimensions of the deposited layers are crucial for achieving this accuracy. The width and height of the deposited layers, key indicators of geometric dimensions, directly affect the forming precision. This study conducted experiments and in-depth analysis to investigate the influence of various process parameters on these dimensions and proposed a predictive model for accurate forecasting. It was found that the width of the deposited layers was positively correlated with laser power and arc current and negatively correlated with scanning speed, while the height was negatively correlated with laser power and scanning speed and positively with arc current. Quantitative analysis using the Taguchi method revealed that the arc current had the most significant impact on the dimensions of the deposited layers, followed by scanning speed, with laser power having the least effect. A predictive model based on extreme gradient boosting (XGBoost) was developed and optimized using particle swarm optimization (PSO) for tuning the number of leaf nodes, learning rate, and regularization coefficients, resulting in the PSO-XGBoost model. Compared to models enhanced with PSO-optimized support vector regression (SVR) and XGBoost, the PSO-XGBoost model exhibited higher accuracy, the smallest relative error, and performed better in terms of Mean Relative Error (MRE), Mean Square Error (MSE), and Coefficient of Determination R2 metrics. The high predictive accuracy and minimal error variability of the PSO-XGBoost model demonstrate its effectiveness in capturing the complex nonlinear relationships between process parameters and layer dimensions. This study provides valuable insights for controlling the geometric dimensions of the deposited layers in LAHAM.

Relay Annulation of Ammonium Ylides with Oxindole-Derived α,ß-Unsaturated Ketimines: Catalytic Construction of Spiro-polycyclic Oxindoles.

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls.

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

Intrarenal pH-Responsive Self-Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury.

Metabolic acidosis-induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end-stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH-responsive luminescent gold nanoparticles (p-AuNPs) in the second near-infrared emission co-coated with 2,3-dimethylaleic anhydride conjugated ß-mercaptoethylamine and cationic 2-diethylaminoethanethiol hydrochloride, which showed sensitive pH-induced charge reversal and intrarenal self-assembly for highly sensitive and long-time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH-induced intrarenal self-assembly and enhanced interactions between pH-triggered positively charged p-AuNPs and renal tubular cells, the early- and late-stage MAKI could be differentiated rapidly within 10 min post-injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p-AuNPs were demonstrated to effectively real-time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH-responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early-stage diagnosis of pH-related diseases.

Noncovalent Interaction Guided Precise Photoluminescence Regulation of Gold Nanoclusters in Both Isolate Species and Aggregate States.

Designing luminophores bright in both isolate species and aggregate states is of great importance in many emerging cutting-edge applications. However, the conventional luminophores either emit in isolate species but quench in aggregate state or emit in aggregate state but darken in isolate species. Here we demonstrate that the precise regulation of noncovalent interactions can realize luminophores bright in both isolate species and aggregate states. It is firstly discovered that the intra-cluster interaction enhances the emission of atomically precise Au25(pMBA)18 (pMBA=4-mercaptobenzoic acid), a nanoscale luminophore, while the inter-cluster interaction quenches the emission. The emission enhancing strategies are then well-designed by both introducing exogenous substances to block inter-cluster interaction and surface manipulation of Au25(pMBA)18 at the molecular level to enhance intra-cluster interaction, opening new possibilities to controllably enhance the luminophore's photoluminescence in both isolate species and aggregate states in different phases including aqueous solution, solid state and organic solvents.

Modular Assembly of 2-Aminoaniline Derivatives by Merging Hydroxylamine-Passerini and Hetero-Cope Rearrangement.

A metal-free three-component protocol that combines a hydroxylamine-Passerini reaction and hetero-Cope rearrangement was realized, which enables the modular assembly of a wide range of structurally new and interesting 2-aminoanilines bearing an α-hydroxyamide substructure.

Transcytosis-Based Renal Tubular Reabsorption of Luminescent Gold Nanoparticles for Enhanced Tumor Imaging.

Transcytosis-based tubular reabsorption of endogenous proteins is a well-known energy-saving pathway that prevents nutrient loss. However, utilization of this well-known reabsorption pathway for the delivery of exogenous nanodrugs remains a challenge. In this study, using the surface mimic strategy of a specific PEPT1/2-targeted Gly-Sar peptide as a ligand, renal-clearable luminescent gold nanoparticles (P-AuNPs) were developed as protein mimics to investigate the transcytosis-based tubular reabsorption of exogenous substances. By regulating the influential factors (H+ content in tubular lumens and PEPT1/2 transporter counts in tubular cells) of Gly-Sar-mediated transcytosis, the specific and efficient interaction between P-AuNPs and renal tubular cells was demonstrated both in vitro and in vivo. Efficient transcellular transportation significantly guided the reabsorption of P-AuNPs back into the bloodstream, which enhanced the blood concentration and bioavailability of nanoparticles, contributing to high-contrast tumor imaging.

Exploration of quality variation and stability of hybrid rice under multi-environments.

Improving quality is an essential goal of rice breeding and production. However, rice quality is not solely determined by genotype, but is also influenced by the environment. Phenotype plasticity refers to the ability of a given genotype to produce different phenotypes under different environmental conditions, which can be a representation of the stability of traits. Seven quality traits of 141 hybrid combinations, deriving from the test-crossing of 7 thermosensitive genic male sterile (TGMS) and 25 restorer lines, were evaluated at 5 trial sites with intermittent sowing of three to five in Southern China. In the Yangtze River Basin, it was observed that delaying the sowing time of hybrid rice combinations leads to an improvement in their overall quality. Twelve parents were identified to have lower plasticity general combing ability (GCA) values with increased ability to produce hybrids with a more stable quality. The parents with superior quality tend to exhibit lower GCA values for plasticity. The genome-wide association study (GWAS) identified 13 and 15 quantitative trait loci (QTLs) associated with phenotype plasticity and BLUP measurement, respectively. Notably, seven QTLs simultaneously affected both phenotype plasticity and BLUP measurement. Two cloned rice quality genes, ALK and GL7, may be involved in controlling the plasticity of quality traits in hybrid rice. The direction of the genetic effect of the QTL6 (ALK) on alkali spreading value (ASV) plasticity varies in different cropping environments. This study provides novel insights into the dynamic genetic basis of quality traits in response to different cropping regions, cultivation practices, and changing climates. These findings establish a foundation for precise breeding and production of stable and high-quality rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01442-3.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level.

Ultrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure-property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411-functionalized AuNPs (AS1411-AuNPs, ≈1.8 nm) with emission at 1030 nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor-targeting efficiencies but also the subcellular transport of AS1411-AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.

Cell response and bone ingrowth to 3D printed Ti6Al4V scaffolds with Mg-incorporating sol-gel Ta2O5 coating.

In recent years, additive manufacturing techniques have been used to fabricate 3D titanium (Ti)-based scaffolds for production of desirable complex shapes. However, insufficient osteointegration of porous Ti-based scaffolds can elicit long-term complications (e.g., aseptic loosening) and need further revision surgery. In this study, a magnesium (Mg)-incorporating tantalum (Ta) coating was deposited on a 3D Ti6Al4V scaffold using a sol-gel method for enhancing its osteogenic properties. To evaluate the biofunction of this surface, bone mesenchymal stem cells and rabbit femoral condyle were used to assess the cell response and bone ingrowth, respectively. Ta2O5 coatings and Mg-incorporating Ta2O5 coatings were both homogeneously deposited on porous scaffolds. In vitro studies revealed that both coatings exhibit enhanced cell proliferation, ALP activity, osteogenic gene expression and mineralization compared with the uncoated Ti6Al4V scaffold. Especially for Mg-incorporating Ta2O5 coatings, great improvements were observed. In vivo studies, including radiographic examination, fluorochrome labeling and histological evaluation also followed similar trends. Also, bone ingrowth to scaffolds with Mg-incorporating Ta2O5 coatings exhibited the most significant increase compared with uncoated and Ta2O5 coated scaffolds. All the above results indicate that Mg-doped Ta2O5 coatings are an effective tool for facilitating osteointegration of conventional porous Ti6Al4V scaffolds.

Hypoglossal nerve delineation in nasopharyngeal carcinoma patients may reduce the radiation dose and damage to the nerve.

This study aims to establish a delineation guideline for the contouring of the hypoglossal nerve by dividing the nerve into different segments, and to test the possibility of a radiation dose reduction to the hypoglossal nerve in NPC patients receiving radiotherapy. Twenty NPC patients were selected arbitrarily. The hypoglossal nerves were delineated using anatomic landmarks and divided into the cisternal, intracanalicular, carotid, and transverse segments. The tumor coverage by radiation and dose-volume parameters of the nerve with and without various dose constraints to the hypoglossal nerve were compared. The hypoglossal nerve, which is invisible on CT images, can be delineated accurately with the assistance of several anatomic landmarks. Without a dose constraint to the hypoglossal nerve, the carotid space, intracanalicular, and transverse segments had high radiation dose-volumes. The dose-volume to the nerve, however, can be reduced when the nerve was defined and a dose constraint was given. The delineation of the hypoglossal nerve with its different segments is feasible. The carotid space, intracanalicular, and transverse segments received the highest dose, where the nerve damage was most likely located. The dose to the nerve can be reduced to less than 70 Gy using the intensity-modulated radiotherapy technique.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Pancreatic Cancer and its Attributable Risk Factors in East Asia, Now and Future.

BACKGROUND: The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. METHOD: Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. RESULTS: Pancreatic cancer mortality in males in Japan (2012-2019, APC = -0.97) and Korea (2012-2019, APC = -0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. CONCLUSION: Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.

Mechanical Performance and Chloride Penetration of Calcium Sulfoaluminate Concrete in Marine Tidal Zone.

The enhancement of the durability of sulfoaluminate cement (CSA) in marine environments is of great importance. To this end, an investigation was carried out involving the placement of CSA concrete in the tidal zone of Zhairuoshan Island, Zhoushan, China, and subjected to a 20-month marine tidal exposure test. The comparison was made with ordinary Portland cement (OPC) concrete to evaluate the effectiveness of the former. The test findings indicate that the compressive strength of both types of concrete is reduced by seawater dry-wet cycling, and the porosity of the surface concrete is increased. However, the compressive strength of CSA concrete is observed to be more stable under long-term drying-wetting cycles. When the ettringite in the CSA surface concrete is decomposed due to carbonization and alkalinity reduction, its products will react with Ca2+ and SO42- in seawater to regenerate ettringite to fill in the concrete pores, making the concrete strength more stable and hindering chlorine penetration. Furthermore, CSA concrete exhibits a higher capillary absorption capacity than OPC concrete, which results in chloride accumulation on its surface. However, the diffusion capacity of chloride in CSA concrete is significantly lower than that in OPC concrete.

Glutathione-Activated Emission of Ultrasmall Gold Nanoparticles in the Second Near-Infrared Window for Imaging of Early Kidney Injury.

Biomarker-activatable luminescent probes with high sensitivity and specificity show great promise in advanced bioimaging applications. However, the lack of stable biomarkers at an early stage is currently a major obstacle for sensitive early disease imaging. Herein, we develop a facile in vivo ligand exchange strategy to achieve renal-clearable activatable luminescent gold nanoparticles (AuNPs), which are independent of biomarkers for sensitive and long-time imaging of early kidney injury. Significantly activated emission in the second near-infrared region (∼1026 nm) is realized from the ligand exchange of triphenylphosphine-3,3',3″-trisulfonic acid (TPPTS)-coated AuNPs (∼1.4 nm, TPPTS-AuNPs) with quantitative amounts of glutathione (GSH). The abundant GSH in cells, particularly in liver sinusoids, is then demonstrated successfully to activate the emission of TPPTS-AuNPs with an extremely low background for both cell imaging and in vivo visualization of visceral organs (e.g., liver and kidneys). In addition, the in vivo GSH-exchanged TPPTS-AuNPs show enhanced interactions with acidic renal tubular epithelial cells, resulting in sensitive (contrast index, ∼3.9) and long-time (>6.5 h) noninvasive monitoring of acidosis-induced early kidney injury. This facile ligand exchange strategy opens new possibilities for designing activatable luminescent probes independent of biomarkers for earlier disease diagnosis and treatment.