Pegylated liposomal doxorubicin in partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer: a prospective study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. METHODS: Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval. RESULTS: Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed. CONCLUSION: PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962.

Spatially resolved metabolomics: From metabolite mapping to function visualising.

Mass spectrometry imaging (MSI)-based spatially resolved metabolomics addresses the limitations inherent in traditional liquid chromatography-tandem mass spectrometry (LC-MS)-based metabolomics, particularly the loss of spatial context within heterogeneous tissues. MSI not only enhances our understanding of disease aetiology but also aids in the identification of biomarkers and the assessment of drug toxicity and therapeutic efficacy by converting invisible metabolites and biological networks into visually rendered image data. In this comprehensive review, we illuminate the key advancements in MSI-driven spatially resolved metabolomics over the past few years. We first outline recent innovations in preprocessing methodologies and MSI instrumentation that improve the sensitivity and comprehensiveness of metabolite detection. We then delve into the progress made in functional visualization techniques, which enhance the precision of metabolite identification and annotation. Ultimately, we discuss the significant potential applications of spatially resolved metabolomics technology in translational medicine and drug development, offering new perspectives for future research and clinical translation. HIGHLIGHTS: MSI-driven spatial metabolomics preserves metabolite spatial information, enhancing disease analysis and biomarker discovery. Advances in MSI technology improve detection sensitivity and accuracy, expanding bioanalytical applications. Enhanced visualization techniques refine metabolite identification and spatial distribution analysis. Integration of MSI with AI promises to advance precision medicine and accelerate drug development.

The intestinal absorption of triptolide for the treatment of rheumatoid arthritis is mediated by transporters.

Tripterygium wilfordii Hook. f. is a traditional Chinese herb that is used to treat rheumatoid arthritis (RA). Triptolide (TP), an epoxidized diterpene lactone extracted from this herb, has been suggested to be the primary active and toxic component. In this work, the material basis and molecular mechanism of toxicity induced by T. wilfordii preparations in RA were investigated. Female rats with collagen-induced arthritis were given 500 µg·kg-1 TP intragastrically or intravenously. Compared with that in the control group, the AUClast in the CIA group was 1.7-fold greater after intragastric administration, while this value decreased 22.6 % after intravenous administration, suggesting that the absorption of TP was significantly greater in the CIA group. The results from RT-PCR and probe substrate perfusion indicated that Oatp1a5 expression was upregulated while P-glycoprotein (P-gp) expression was downregulated in the duodenums of CIA rats. Naringin, an inhibitor of Oatp1a5, decreased the Peff of TP in the rat duodenum by 27.9 %, whereas verapamil hydrochloride, an inhibitor of P-gp, increased the Peff by 50.8 %, suggesting that Oatp1a5 and P-gp mediate the uptake and efflux of TP in the rat duodenum, respectively. Furthermore, among the upstream nuclear receptors, the mRNA expression levels and protein expression levels of FXR and VDR were noticeably decreased. In the present study, the absorption of TP in the duodenums of CIA rats significantly increased due to the upregulation of Oatp1a5 expression and the downregulation of P-gp expression, leading to an increase in TP plasma exposure after intragastric administration. The altered expression of Oatp1a5 and P-gp may be related to FXR and VDR.

Dynamic role of exosomal long non-coding RNA in liver diseases: pathogenesis and diagnostic aspects.

BACKGROUND: Liver disease has emerged as a significant health concern, characterized by high rates of morbidity and mortality. Circulating exosomes have garnered attention as important mediators of intercellular communication, harboring protein and stable mRNAs, microRNAs, and long non-coding RNAs (lncRNA). This review highlights the involvement of exosomal lncRNA in the pathogenesis and diagnosis of various liver diseases. Notably, exosomal lncRNAs exhibit therapeutic potential as targets for conditions including hepatic carcinoma, hepatic fibrosis, and hepatic viral infections. METHOD: An online screening process was employed to identify studies investigating the association between exosomal lncRNA and various liver diseases. RESULT: Our study revealed a diverse array of lncRNAs carried by exosomes, including H19, Linc-ROR, VLDLR, MALAT1, DANCR, HEIH, ENSG00000248932.1, ENST00000457302.2, ZSCAN16-AS1, and others, exhibiting varied levels across different liver diseases compared to normal liver tissue. These exosomal-derived lncRNAs are increasingly recognized as pivotal biomarkers for diagnosing and prognosticating liver diseases, supported by emerging evidence. However, the precise mechanisms underlying the involvement of certain exosomal lncRNAs remain incompletely understood. Furthermore, the combined analysis of serum exosomes using ENSG00000258332.1, LINC00635, and serum AFP may serve as novel and valuable biomarker for HCC. Clinically, exosomal ATB expression is upregulated in HCC, while exosomal HEIH and RP11-513I15.6 have shown potential for distinguishing HCC related to HCV infection. CONCLUSION: The lack of reliable biomarkers for liver diseases, coupled with the high specificity and sensitivity of exosomal lncRNA and its non-invasive detection, promotes exploring their role in pathogenesis and biomarker for diagnosis, prognosis, and response to treatment liver diseases.

A postmortem high-resolution MRI study of the development of cochlear nerve-related structures in the second and third trimesters of pregnancy.

Background: Magnetic resonance imaging (MRI) is used to determine whether cochlear nerve development is normal in infants and adults, but it has not yet been used to evaluate cochlear nerve development or measure cochlear nerve-related structures in the fetus. This study sought to provide imaging data for clinical evaluations concerning cochlear nerve development in the fetus using MRI. Methods: Postmortem 3.0-Tesla MRI of inner ear was performed in 51 fetuses with normal temporal bones at 25 to 40 weeks of gestation. The continuous scanning protocol incorporated axial three-dimensional (3D) sampling perfection with application-specific contrasts using different flip angle evolution sequences. The images were evaluated to measure the structures of the cochlear aperture (CA), internal auditory canal (IAC), and vestibulocochlear and facial nerves in the cerebellopontine angle (CPA), which have been reported to be associated with cochlear nerve development. We also calculated the ratio between the diameters of the vestibulocochlear and facial nerves. The measurable parameters were compared between the right and left sides. The threshold for statistical significance was set at P<0.05. Results: The inner ear anatomy was discernible on MRI in all the fetal specimens, and growth of the CA, IAC, vestibulocochlear nerve, and facial nerve in the CPA was observed as fetal age increased. There was no significant difference in the measurements of these structures between the right and left sides (all P>0.05). Conclusions: MRI can be used to help evaluate the anatomy and development of the cochlear nerve in the fetus. These normative measurements could be valuable for clinical evaluations of the cochlear nerve.

Identification of chemical constituents and pharmacokinetic characteristics of Xiaoyan Tuire Granule in rats.

Xiaoyan Tuire Granule is a type of Chinese patent medicine that has been proven effective in treating respiratory tract infections. However, while it has been successfully introduced into clinical use, more knowledge is still needed regarding its chemical components and pharmacokinetics. This study investigated the chemical profile in the medicine and rat plasma by ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Orbitrap-MS/MS). Subsequently, it developed a validated ultra high-performance liquid chromatography coupled with quadrupole mass spectrometry (UHPLC-MS/MS) method for determining five components in rat plasma after oral administration of Xiaoyan Tuire Granule. As a result, a total of 106 constituents were inferred, including 9 terpenoids, 29 flavonoids, 33 organic acids, 12 phenylpropanoids and 23 other compounds. After administration, 86 compounds were inferred in rat plasma, including 73 prototypes and 13 metabolites. The metabolic pathways were primarily hydrogenation, glucuronic acid conjugation, sulfate conjugation, hydrolysis and methylation. The established method determined the contents of esculetin, esculin, isovitexin, caffeic acid and p-coumaric acid had a good separation, and all the legal verification met the requirements. The pharmacokinetic results indicate that the absorption rate of the five compounds in vivo was rapid, with a Tmax of less than 0.25 h, and the elimination rate was also fast, with a half-time (T1/2) ranging from 1.22 h to 2.19 h. It is worth noting that esculin and esculetin have similar half-time in vivo due to their structural similarities. Among these five compounds, the AUC0-∞ and MRT0-∞ of p-coumaric acid and esculetin were relatively higher, indicating higher exposure and longer residence time of both compounds in vivo. In conclusion, this paper researched the chemical constituents and pharmacokinetics of Xiaoyan Tuire Granule, which provided the reference for further study.

Patch and matrix striatonigral neurons differentially regulate locomotion.

The striatonigral neurons are known to promote locomotion1,2. These neurons reside in both the patch (also known as striosome) and matrix compartments of the dorsal striatum3-5. However, the specific contribution of patch and matrix striatonigral neurons to locomotion remain largely unexplored. Using molecular identifier Kringle-Containing Protein Marking the Eye and the Nose (Kremen1) and Calbidin (Calb1)6, we showed in mouse models that patch and matrix striatonigral neurons exert opposite influence on locomotion. While a reduction in neuronal activity in matrix striatonigral neurons precedes the cessation of locomotion, fiber photometry recording during self-paced movement revealed an unexpected increase of patch striatonigral neuron activity, indicating an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed locomotion, contrasting with the locomotion-promoting effect of matrix striatonigral neurons. Consistently, patch striatonigral neuron activation markedly inhibited dopamine release, whereas matrix striatonigral neuron activation initially promoted dopamine release. Moreover, the genetic deletion of inhibitory GABA-B receptor Gabbr1 in Aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neurons (DANs) completely abolished the locomotion-suppressing effect caused by activating patch striatonigral neurons. Together, our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting the activity of ALDH1A1+ nigrostriatal DANs.

Dose-response relationship between physical activity and frailty: A systematic review and meta-analysis.

Objective: Frailty is a significant public health issue facing aging societies and can be reduced by physical activity (PA), but the dose-response relationship between PA and frailty is not clear. This systematic review and dose-response meta-analysis aimed to assess the effect of PA on frailty in adults by aggregating data from observational studies. Methods: PubMed, Embase, Web of Science, Cochrane Library, Scopus, SAGE Reference Online, SinoMed, CINAHL and CNKI were retrieved for articles published before May 2024. After quality evaluation, data on PA and the risk of frailty were extracted. Stata/MP 17.0 was used for dose-response meta-analysis. Results: A total of 15 articles were included, involving 34,754 participants, including 4250 subjects with frailty or pre-frailty. The consequence of the dose-response meta-analysis revealed that compared with those who were not active at all, a 22 % (95 % CI, 16 %-28 %) reduction in the risk of frailty in individuals with 11.25 MET h/week of cumulative activity and a 55 % (95 % CI, 44 %-63 %) reduction in the risk of frailty in those with 22.5 MET h/week of cumulative activity; for higher activity levels (36.75 MET h/week), the risk of frailty was reduced by 68 % (95 % CI, 58 %-76 %) and continued to be reduced as PA volum increased. Conclusions: There is a non-linear dose-response relationship between PA and frailty risk. Even small amounts of PA could reduce the risk of frailty. Meeting the minimum recommended PA target could reduce some risks, and doubling the recommended PA volumes could reduce most risks, which continue to increase as the volum of PA accumulates.

Adaptability, Scalability and Sustainability (ASaS) of complex health interventions: a systematic review of theories, models and frameworks.

BACKGROUND: Complex health interventions (CHIs) are increasingly used in public health, clinical research and education to reduce the burden of disease worldwide. Numerous theories, models and frameworks (TMFs) have been developed to support implementation of CHIs. This systematic review aims to identify and critique theoretical frameworks concerned with three features of implementation; adaptability, scalability and sustainability (ASaS). By dismantling the constituent theories, analysing their component concepts and then exploring factors that influence each theory the review team hopes to offer an enhanced understanding of considerations when implementing CHIs. METHODS: This review searched PubMed MEDLINE, CINAHL, Web of Science, and Google Scholar for research investigating the TMFs of complex health interventions. Narrative synthesis was employed to examine factors that may influence the adaptability, scalability and sustainability of complex health interventions. RESULTS: A total of 9763 studies were retrieved from the five databases (PubMed, MEDLINE, CINAHL, Web of Science, and Google Scholar). Following removal of duplicates and application of the eligibility criteria, 35 papers were eligible for inclusion. Influencing factors can be grouped within outer context (socio-political context; leadership funding, inter-organisational networks), inner context; (client advocacy; organisational characteristics), intervention characteristics (supervision, monitoring and evaluation), and bridging factors (individual adopter or provider characteristics). CONCLUSION: This review confirms that identified TMFS do not typically include the three components of adaptability, scalability, and sustainability. Current approaches focus on high income countries or generic "whole world" approaches with few frameworks specific to low- and middle-income countries. The review offers a starting point for further exploration of adaptability, scalability and sustainability, within a low- and middle-income context. TRIAL REGISTRATION: Not registered.

Dual-modal imaging-guided agent based on NIR-II aggregation-induced emission luminogens with balanced phototheranostic performance.

Phototherapy has garnered considerable interest for its potential to revolutionize conventional cancer treatment. Organic materials with near-infrared II (NIR-II, 1000-1700 nm) fluorescence and photothermal effects are key for precise tumor diagnosis and treatment, yet optimizing their output for higher resolution and reduced photodamage remains a challenge. Herein, a multifunctional NIR-II photosensitizer (LSC) has been developed using the aggregation-induced emission (AIE) technology. The utilization of thieno[3,2-b]thiophene as an electron-rich and bulky donor/acceptor bridge has allowed for the elongation of conjugation length and distortion of the AIE main chain. This strategic modification effectively enhances the electron push-pull effect, endowing the LSC with a Stokes shift of over 400 nm and AIE characteristics. We have successfully built-up stable nanoparticles called FA-LSC NPs using a nano-precipitation method. These nanoparticles exhibit high NIR-II fluorescent brightness (ε × QY = 1064 M-1 cm-1) and photothermal conversion efficiency (41%). Furthermore, the biocompatible FA-LSC NPs demonstrate effective tumor accumulation and exceptional photothermal therapeutic efficacy both in vitro and in vivo. These nanoparticles were applied to fluorescence-photothermal dual-mode imaging-guided photothermal ablation in a HeLa tumor xenograft mouse model, resulting in favorable photothermal clearance outcomes.

Effects of polyvinyl chloride microplastics and benzylalkyldimethylethyl compounds on system performance, microbial community and resistance genes in sulfur autotrophic denitrification system.

Benzylalkyldimethylethyl ammonium compounds (BAC) and polyvinyl chloride microplastics (PVC MPs), as the frequently detected pollutants in wastewater treatment plants (WWTPs), have attracted more concerns on their ecosystem risks. Therefore, this study investigated how the sulfur autotrophic denitrification (SAD) system responded to the single and joint stress of PVC MPs (1, 10 and 100 mg/L) and BAC (0.5, 5 and 10 mg/L). After 100 days of operation, the presence of 10 mg/L BAC led to obviously inhibitory effects on system performance and microbial metabolic activity. And the additions of PVC MPs or/and BAC stimulated the proliferation of intracellular resistance genes (RGs), whereas exposure to BAC increased the abundances of extracellular RGs and free RGs in water more significantly. Compared to the joint stress, BAC single stress resulted in higher abundances of free RGs in water, which further increased the risk of RGs propagation. Moreover, the interaction between mobile genetic elements and extracellular polymeric substances further increased the spread of RGs. Pathogens might be the potential hosts of RGs and enriched in SAD system and plastisphere, thereby leading to more serious ecological risks. This study will broaden the understanding of the environmental hazards posed by PVC MPs and BAC in WWTPs.

Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Transferability and Accuracy of Ionic Liquid Simulations with Equivariant Machine Learning Interatomic Potentials.

Ionic liquids (ILs) are an exciting class of electrolytes finding applications in many areas from energy storage to solvents, where they have been touted as "designer solvents" as they can be mixed to precisely tailor the physiochemical properties. As using machine learning interatomic potentials (MLIPs) to simulate ILs is still relatively unexplored, several questions need to be answered to see if MLIPs can be transformative for ILs. Since ILs are often not pure, but are either mixed together or contain additives, we first demonstrate that a MLIP can be trained to be compositionally transferable; i.e., the MLIP can be applied to mixtures of ions not directly trained on, while only being trained on a few mixtures of the same ions. We also investigated the accuracy of MLIPs for a novel IL, which we experimentally synthesize and characterize. Our MLIP trained on ∼200 DFT frames is in reasonable agreement with our experiments and DFT.

Patch and matrix striatonigral neurons differentially regulate locomotion.

Striatonigral neurons, known to promote locomotion, reside in both the patch and matrix compartments of the dorsal striatum. However, their compartment-specific contributions to locomotion remain largely unexplored. Using molecular identifier Kremen1 and Calb1 , we showed in mouse models that patch and matrix striatonigral neurons exert opposite influences on locomotion. Matrix striatonigral neurons reduced their activity before the cessation of self-paced locomotion, while patch striatonigral neuronal activity increased, suggesting an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed ongoing locomotion with reduced striatal dopamine release, contrasting with the locomotion-promoting effect of matrix striatonigral neurons, which showed an initial increase in dopamine release. Furthermore, genetic deletion of the GABA-B receptor in Aldehyde dehydrogenase 1A1-positive (ALDH1A1 + ) nigrostriatal dopaminergic neurons completely abolished the locomotion-suppressing effect of patch striatonigral neurons. Our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting ALDH1A1 + nigrostriatal dopaminergic neurons.

Exploring the gut microbiota mediated biotransformation of Senecio scandens Buch.-Ham.: Insights from metabolite spectrum with UHPLC-Q-Orbitrap HRMS and bioinformatics analysis of gut microbiota metabolites.

Senecio scandens Buch.-Ham., a traditional Chinese medicine commonly used clinically, exhibits various pharmacological properties, including anti-inflammatory, anti-tumor, antiviral, and antibacterial activities. However, its water extracts' chemical components and metabolites are inadequately understood, limiting further research. In this study, the chemical components and metabolism processes of Senecio scandens, both in vivo (plasma, feces, urine, and bile) and in vitro (gut microbiota and liver microsomes), were characterized based on ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry. Additionally, metabolites detectable in fecal samples and intestinal microbiota incubated but absent in liver microsomes were identified as characteristic metabolites of intestinal microbiota. The targets of the characteristic metabolites of intestinal microbiota were collected, followed by exploration of potential pathways through KEGG enrichment analysis. As a result, a total of 133 chemical components were preliminarily identified, including 35 organic acids, 21 alkaloids, 19 flavonoids and their glycosides, 17 phenylpropanoids, 10 jacaranda ketones, and 31 other compounds. Notably, 12 of these were potentially novel compounds. In addition, 39 prototype components in rats and 109 metabolites were identified and characterized, including 102 in vivo and 52 metabolites in vitro (51 in rat gut microbiota and 24 in rat liver microsomes). The main metabolic pathways include oxidation, reduction, hydrolysis, methylation, glucuronidation, sulfonation, and acetylation reactions. Furthermore, KEGG enrichment analysis revealed that the characteristic metabolites of intestinal microbiota may be related to the ErbB, FoxO, mTOR, and MAPK signaling pathways, exhibiting anti-inflammatory and anti-tumor effects. In summary, the chemical components and metabolites of Senecio scandens were comprehensively identified using a rapid and accurate method, providing a scientific basis for the in-depth study of the material basis and its clinical application of Senecio scandens.

Integrated metabolomics and network pharmacology approach to exploring the anti-inflammatory mechanisms of Chuanwang xiaoyan capsules.

Chuanwang xiaoyan capsules (CWXYC) have anti-inflammatory and detoxification effect, are used in the treatment of acute and chronic tonsillitis, pharyngitis and other inflammation-related diseases clinically. However, the anti-inflammatory mechanisms have not been elucidated. This study aimed to investigate the anti-inflammatory mechanisms of CWXYC using cell metabolomics and network pharmacology strategy. Specifically, CWXYC could efficiently reduce the content of nitric oxide (NO), the cytokines Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in LPS-induced RAW264.7 cells. Furthermore, metabolomics was performed to achieve 23 differential metabolites and 9 metabolic pathways containing glutamate metabolism, glutathione metabolism, arginine and proline metabolism, urea cycle, malate-aspartate shuttle, phosphatidylcholine biosynthesis, transfer of acetyl groups into mitochondria, cysteine metabolism and ammonia recycling. The results of network pharmacology showed that CWXYC could treat inflammation through 10 active components, 10 key targets and 55 pathways. Then the results of molecular docking also approved that there existed strong binding energy between the active components and the key targets. Finally, metabolomics and network pharmacology were integrated to get core targets AKT1, SRC and EGFR. Western blot experiments verified that CWXYC could exert anti-inflammatory effect by down-regulating the activated Akt1 and Src proteins. This study demonstrated that CWXYC exerted effects against inflammation, and the potential mechanisms were elucidated. These novel findings will provide an important basis for further mechanism investigations.

High-Fidelity Spatiotemporal Recognition of Golgi ALP through an Initial-Accumulation and Postactivation Strategy.

Various signal molecules mediate complex physiological processes collectively in the Golgi. However, most currently accessible probes are questionable in illuminating the functions of these reactive species in Golgi because of the inability to irradiate these probes only at the desired Golgi location, which compromises specificity and accuracy. In this study, we rationally designed the first photocontrollable and Golgi-targeted fluorescent probe to in situ visualize the Golgi alkaline phosphatase (ALP). The designed probe with natural yellow fluorescence can provide access into Golgi and monitor the exact timing of accumulation in Golgi. On-demand photoactivation at only the desired Golgi location affords a significant emission response to ALP with illuminating red fluorescence at 710 nm. Through the photocontrollable fluorescence responsiveness to ALP, precise spatiotemporal recognition of Golgi ALP fluctuations is successfully performed. With this probe, for the first time, we revealed the Golgi ALP levels during cisplatin-induced acute kidney injury (AKI), which will further facilitate and complement the comprehensive exploration of ALP kinetics during physiological and pathological processes.