Objective To investigate the value of Contrast-Enhanced Ultrasound (CEUS) combined with Procalcitonin (PCT) in differentiating Tuberculous Lymph Nodes (TLN) from Metastatic Lymph Nodes (MLN). Methods This prospective cohort study included 207 consecutive patients diagnosed with CTL. Before confirming through pathology or laboratory tests, every patient received standard ultrasound, CEUS, and MRI examinations, with the imaging results analyzed afterward. Serum indicators were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Predictive modeling was performed by multifactorial logistic regression. Evaluate the diagnostic and calibration performance of the predictive model by drawing Receiver Operating Characteristic (ROC) curves and calibration curves, and using Area Under the Curve (AUC) and Hosmer-Lemeshow (H-L) tests. Results The presence of lymph node lesions was confirmed by routine ultrasound and MRI in 207 patients, of which 102 (49.27 %) had a pathological or laboratory diagnosis of metastatic lymph nodes (MLN), and 50.8 % were tuberculous lymph nodes (TLN). According to imaging findings of CEUS, TLN was more commonly associated with enhanced concentric performance in the arterial phase (67.65 % vs. 40.95 %) and heterogeneous enhancement pattern in lymph nodes (70.59 % vs. 52.38 %). Peak Intensity (PI) of lesions was higher in patients with MLN. Increased age-enhanced concentric performance in the arterial phase, increased PI, and serum PCT greater than 5.39 ng/mL were independent risk factors for MLN. The prediction model of serum PCT combined with CEUS had a higher diagnostic value for MLN. The H-L test indicated a satisfactory model fit (all p > 0.05), and the calibration curve closely approximates the ideal diagonal. Conclusion CEUS combined with serum PCT has better clinical application value in the differential diagnosis of TLN and MLN.

Video shows displacement of Lat-M cells in cell competition. Lat-M cells (Green) surrounded by PA (Red) cells being displaced under cell competition assay conditions.

Objective: To evaluate the application value of combining spectral imaging and metal artifact reduction (MAR) in head and neck CTA after the embolization of intracranial aneurysms. Methods: We collected 37 patients who experienced embolization of intracranial aneurysms then received spectral imaging of head and neck CTA. Monochromatic images with energy ranging from 70～140 keV, 120 kVp-like mixed energic images, 70～140 keV MAR images, and 120 kVp-like MAR images were generated. The region of interest was placed on the area near the coil and with the most serious metal artifact. CT attenuation and standard deviation were measured, and artifact index (AI) and signal-noise ratio (SNR) were calculated. Two radiologists independently subjectively evaluated the metal artifact and the display of surrounding vessels using Likert 5 scales. The subjective scores and objective parameters between MAR and non-MAR images were compared. The Wilcoxon ranking test, paired sample t test, and independent sample t test were utilized to compare parameters between the groups. Results: MAR images had significantly lower AI than did non-MAR images for all eight monochromatic energies. When energies ranged from 80~110 keV, SNR was higher for MAR images than for non-MAR images, and the difference was statistically significant. With same energies, MAR images had higher artifact and vessel display scores than did non-MAR images. For non-MAR images, the different coil diameters did not make a statistical difference in AI and vessel display scores. For MAR images, a larger coil diameter (>8.79 mm) led to higher AI and lower vessel display scores than did normal diameters (≤8.79 mm). Conclusion: The combination of spectral imaging and MAR could effectively reduce the metal artifact of implants for the embolization of intracranial aneurysms and improve the surrounding vessel display. Moreover, the metal artifact reduction effect was more significant for the coils with smaller diameters.

Pidotimod is a chiral drug that possesses two chiral centers, resulting in three isomeric impurities (analytes, A). This study employs electrospray ionization ion trap mass spectrometry (ESI-MS) through collision-induced dissociation (CID) to investigate the chiral recognition of pidotimod and its three isomers to eliminate chromatographic separation. Three approaches were explored: (1) Protonated molecules in CID exhibited discriminative potential for diastereomers, with the ability to distinguish between S,S and R,R configurations, albeit with an Rchiral value of ~1.8. However, differentiation between R,S and S,R configurations was not achievable. (2) Alkali adductions (lithium and sodium) only discerned diastereomers. The Rchiral values of the diastereomers obtained from alkali adduct ions were significantly lower than those obtained from protonated ions. (3) Therefore, a third approach was used to address the challenge of distinguishing between R,S and S,R configurations, including the introduction of chiral references (ref) and transition metals (MII) to form metal-bound complexes [MII(A)(ref)-H]+. Additionally, we synthesized a novel ligand, 4-(N-tert-butoxycarbonyl [Boc]-L-prolinamido)phenol (denoted as ligand A), by modifying N-t-Boc-L-Pro with 2-aminophenol, which, in combination with CuII and NiII, enabled simultaneous differentiation of all four isomers. CuII complexes exhibited significant chiral selectivity between R,S and S,R configurations. Density functional theory calculations were performed to further elucidate the stereodynamic behavior and stoichiometry of these ions in the gas phase. These calculations revealed the interaction energy and coordination sites of the precursor ions in the gas phase, correlating well with MS/MS experiment results. Additionally, the logarithm of the CuII complexes' characteristic fragment ion abundance ratio demonstrated a strong linear relationship with enantiomeric excess (ee). This study presents a novel strategy for chiral drug quality control that eliminates chromatographic separation.

Objective Aortic Dissection (AD) is one of the most fatal acute diseases in cardiovascular diseases, with rapid onset and progression and a high fatality rate. This study aims to investigate the clinical values of non-enhancement peripheral pulse-gating rapid magnetic resonance imaging in deterministic diagnosis of AD. Methods Aorta magnetic resonance imaging was performed in 21 healthy volunteers at a 1.5t MR scanner sequences including cardiac-gated and peripheral pulse-gated True-FISP and HASTE were carried out separately. Acquisition Time (TA), Signal to Noise Ratio (SNR), Contrast Noise Ratio (CNR), and entirety of vessel wall blood flow artifacts were measured and compared. A total of 56 AD cases were displayed by non-enhancement peripheral pulse-gating fast MR imaging, and the results were compared with pathological findings or CTA of the aorta. The dissection rupture, tear film, true and false lumen, thrombosis, hydropericardium, and the main branches of AD were evaluated respectively. Results There were no significant differences in SNR, CNR, entirety of the vessel wall, and blood flow artifact between cardiac-gated and peripheral pulse-gated fast MR imaging. Non-enhancement pulse-gated fast scanning takes less TA time. By the pulse-gated non-enhancement fast MR imaging, the dissection rupture, tear film, true and false cavity, thrombosis, hydropericardium, and the main branches of aortic dissection were shown clearly. Multi-planar and multi-angle scans helped to show the extent of entrapment rupture, whereas partial complex tears or bi-directional tears were slightly less well visualized. Conclusion Non-enhancement peripheral pulse-gated rapid magnetic resonance imaging can be used for deterministic diagnosis of AD.

Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 μM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX·HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy.

The use of mass spectrometry for chiral recognition and quantification has attracted great interest owing to its speed, sensitivity, specificity, and tolerance. However, searching for chiral selectors in chiral analyses using mass spectrometry is still problematic. In this study, chiral drugs could be applied as references for the chiral recognition and enantiomeric quantification of valsartan and voriconazole. Two novel pairs of metal-bound diastereomeric complex ions were detected by mass spectrometry, namely, nickel (II)-bound dimeric ions [NiII (2R,5S-emtricitabine) (S-valsartan)-H]+ and [NiII (2R,5S-emtricitabine) (R-valsartan)-H]+ and copper (II)-bound dimeric ions [CuII (S,S,S-enalaprilat) (2S,3R-voriconazole)-H]+ and [CuII (S,S,S-enalaprilat) (2R,3S-voriconazole)-H]+ . The resulting diastereomers were successfully identified based on the relative intensities of their characteristic fragments using tandem mass spectrometry. The logarithm of the characteristic fragment ion abundance ratio exhibited a good linear relationship with the enantiomeric excess. Density functional theory calculations were also performed to elucidate the mechanism of the structural differences observed in the MS results. This established approach proves that chiral drugs can serve as ligands for the rapid recognition and quantitative analysis of other chiral drugs without a chiral chromatographic column or complex sample pretreatment.

目的:建立厄贝沙坦原料药和氯沙坦钾原料药中5-[4′-(叠氮甲基)-[1,1′-联苯]-2-基]-1H-四氮唑(MB-X),4′-叠氮甲基-[1,1′-联苯]-2-氰基(AZBC)和5-[4′-[(5-(叠氮甲基)-2-丁基-4-氯-1H-咪唑-1-基)甲基]-[1,1′-联苯]2-基]-1H-四唑(LADX)这3种叠氮类基因毒性杂质的超高效液相色谱-串联(UPLC-MS/MS)三重四级杆质谱的检测方法.方法:ACQUITY UPLC HSS T3(100 mm×2.1 mm,1.8μm)色谱柱;0.1％甲酸水溶液为流动相A,0.1％甲酸的甲醇溶液为流动相B,梯度洗脱;流速为0.35 mL·min-1,柱温为50℃;采用大气压化学离子源(APCI)正/负离子扫描,多反应监测(MRM)模式对3种基因毒性杂质同时进行定量检测.结果:3种杂质在0.5～100 ng·mL-1范围内具有良好的线性关系;检测限分别为0.05,0.03,0.02 ng·mL-1,定量限分别为0.15,0.11,0.08 ng·mL-1;3种杂质在厄贝沙坦原料药中,低、中、高3个浓度的加样回收率(n=3)范围为94.5％ ～103.5％,相对标准偏差(RSD)<3.88％;在氯沙坦钾原料药中,低、中、高3个浓度的加样回收率(n=3)范围为93.8％ ～100.9％,RSD<4.25％.结论:该方法灵敏度高、专属性强,可用于测定厄贝沙坦原料药和氯沙坦钾原料药中3种叠氮类基因毒性杂质,为厄贝沙坦和氯沙坦钾的质量控制提供技术支持.

目的 建立一种用于快速筛查复杂基质中西格列汀的纸喷雾离子化质谱(PSI-MS)方法.方法 采用 PSI-MS 技术,优化喷雾电压、喷雾溶剂、色谱纸尖至质谱锥孔距离、进样方式等实验参数,对复杂基质中的西格列汀进行快速筛查,并通过内标法进行半定量分析.结果 每个样品检测时间小于1 min,西格列汀在0.1～10 μg·mL-1范围内线性关系良好,相关系数 r2 为0.9998,加样回收率实验结果在 94％～109％,并且RSD均小于 5％.结论 本方法操作简便、前处理简单、灵敏度高、重现性好,可用于复杂基质中西格列汀的快速识别及定量.

A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

目的:建立高效液相色谱-三重四极杆质谱(HPLC-MS/MS)法测定盐酸二甲双胍原料药和制剂中N-亚硝基二甲胺(NDMA).方法:采用 Phenomenex ACE Excel 3 C18-AR 色谱柱(100 mm×4.6 mm,3μm),以0.1％甲酸水-0.1％甲酸甲醇为流动相,梯度洗脱,流速0.5 mL·min-1,柱温40℃,进样量5 μL;质谱离子化方式为APCI,正离子模式,多反应监测(MRM),NDMA的定量离子对为m/z 75.0→43.0,定性离子对为m/z 75.0→58.0.结果:NDMA质量浓度在1～100 ng·mL-1范围内,线性关系良好;检测限为0.25 ng·mL-1;30批样品的测定结果NDMA的含量为0～0.46μg·g-1.结论:本方法可用于测定盐酸二甲双胍原料药和制剂中NDMA含量.

目的:考察出现可见异物现象的复方维生素B注射液对家兔股四头肌肌肉刺激现象及刺激物的鉴定.方法:选取2个厂家的出现可见异物现象的复方维生素B注射液进行家兔股四头肌的肌肉刺激实验,对照组为同厂家未检出可见异物的复方维生素B注射液,阳性组为1.7％(w/v)乙酸溶液.选取2个厂家的出现可见异物现象的复方维生素B注射液进行L929细胞毒性实验.通过扫描电镜确定出现可见异物现象的复方维生素B注射液中可见异物的成分.结果:2个厂家的出现可见异物现象的复方维生素B注射液均导致家兔股四头肌产生肌肉刺激和炎症,对照组为阴性.与可见异物未检出的复合维生素B注射液相比,出现可见异物现象的复方维生素B注射液导致L929细胞毒性结果无明显差异.扫描电镜结果筛查出出现可见异物现象的复合维生素B注射液玻璃安瓿瓶的瓶底和内表面出现不同程度的侵蚀和脱片现象.结论:出现可见异物现象的复方维生素B注射液对家兔股四头肌肌肉产生局部刺激和炎症反应,刺激物为安瓿瓶内玻璃片样的脱落物.

Objective:This study aimed to establish a method to predict the overall survival (OS) of patients with stage I-III colorectal cancer (CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification. Methods:We retrospectively identified 161 consecutive patients with stage I-III CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction. Results:The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio (HR)=6.670; 95% confidence interval (95% CI): 3.433-12.956; P<0.001), external validation cohort 1 (HR=2.866; 95% CI: 1.646-4.990; P<0.001) and external validation cohort 2 (HR=3.342; 95% CI: 1.289-8.663; P=0.002). Incorporating the EcoRad signature into the prediction model presented a higher prediction ability (P<0.001) with respect to the C-index (0.813, 95% CI: 0.804-0.822 in the training cohort; 0.758, 95% CI: 0.751-0.765 in the external validation cohort 1; and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis (TNM) system, as well as a better calibration, improved reclassification and superior clinical usefulness. Conclusions:This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage I-III CRC patients.

To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). iEDI successfully classified immune status in Resec1 (AUC 0.771, 95 • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.

BackgroundDespite the well-known role of immunoscore, as a prognostic tool, that appeared to be superior to tumor–node–metastasis (TNM) staging system, no prognostic scoring system based on immunohistochemistry (IHC) staining digital image analysis has been established in non-small cell lung cancer (NSCLC). Hence, we aimed to develop and validate an immune-based prognostic risk score (IMPRS) that could markedly improve individualized prediction of postsurgical survival in patients with resected NSCLC.MethodsIn this retrospective study, complete resection of NSCLC (stage I–IIIA) was performed for two independent patient cohorts (discovery cohort, n=168; validation cohort, n=115). Initially, paraffin-embedded resected specimens were stained by immunohistochemistry (IHC) of three immune cell types (CD3+, CD4+, and CD8+ T cells), and a total of 5,580 IHC-immune features were extracted from IHC digital images for each patient by using fully automated pipeline. Then, an IHC-immune signature was constructed with selected features using the LASSO Cox analysis, and the association of signature with patients’ overall survival (OS) was analyzed by Kaplan–Meier method. Finally, IMPRS was established by incorporating IHC-immune signature and independent clinicopathological variables in multivariable Cox regression analysis. Furthermore, an external validation cohort was included to validate this prognostic risk score.ResultsEight key IHC-immune features were selected for the construction of IHC-immune signature, which showed significant associations with OS in all cohorts [discovery: hazard ratio (HR)=11.518, 95%CI, 5.444–24.368; validation: HR=2.664, 95%CI, 1.029–6.896]. Multivariate analyses revealed IHC-immune signature as an independent prognostic factor, and age, T stage, and N stage were also identified and entered into IMPRS (all p<0.001). IMPRS had good discrimination ability for predicting OS (C-index, 0.869; 95%CI, 0.861–0.877), confirmed using external validation cohort (0.731, 0.717–0.745). Interestingly, IMPRS had better prognostic value than clinicopathological-based model and TNM staging system termed as C-index (clinicopathological-based model: 0.674; TNM staging: 0.646, all p<0.05). More importantly, decision curve analysis showed that IMPRS had adequate performance for predicting OS in resected NSCLC patients.ConclusionsOur findings indicate that the IMPRS that we constructed can provide more accurate prognosis for individual prediction of OS for patients with resected NSCLC, which can help in guiding personalized therapy and improving outcomes for patients.

Background: The stratification of microsatellite instability (MSI) status assists clinicians in making treatment decisions for patients with colorectal cancer (CRC). This study aimed to establish a CT-based radiomics signature to predict MSI status in CRC patients.Methods: A total of 837 CRC patients who underwent preoperative enhanced CT scan and had available MSI status were recruited from two hospitals. Radiomics features were extracted from the segmented tumor, and a series of data balancing and feature selection strategies were used to select MSI-related features. Then, an MSI-related radiomics signature was finally constructed using a genetic algorithm enhanced artificial neural network model. Combined and clinical models were constructed using multivariate logistic regression by integrating with clinical factors with or without the signature. Kaplan-Meier survival analysis was conducted to explore the prognostic information of the signature.Findings: Ten features were selected to construct the signature which showed good performance on both the internal and external validation cohort, with areas under the curve (AUCs) of 0.788 and 0.775, respectively. The performance of the signature was comparable to that of the combined model (AUCs of 0.777 and 0.767) and outperformed the clinical model composed of age and tumor location (AUCs of 0.768 and 0.623). Survival analysis demonstrated that the MSI-related signature could stratify stage II CRC patients in prognosis (HR: 0.402, p = 0.029).Interpretation: This study built a robust radiomics signature with good diagnostic information for MSI status in CRC patients, which may contribute to non-invasive patient classification and assist individualized treatment decisions.Funding Information: This study was supported by the Key R&D Program of Guangdong Province of China [grant number 2021B0101420006], the National Key Research and Development Program of China [grant number 2021YFF1201003], the National Science Fund for Distinguished Young Scholars [grant number 81925023], the National Natural Scientific Foundation of China [grant number 82072090, 81901910, 81771912 and 81901909] and High-level Hospital Construction Project [DFJHBF202105].Declaration of Interests: The authors have declared that no competing interest exists.Ethics Approval Statement: This retrospective study was approved by the Institutional Review Board of the Guangdong Provincial People’s Hospital and the First Affiliated Hospital of Chongqing Medical University. The informed consent forms were waived due to the retrospective nature.

An amphiphilic polymerTNPdemonstrated the formation of a nitroreductase-responsive DOX delivery nanoplatform with high sensitivity and selectivity.

目的:建立高效液相色谱-三重四极杆质谱法分别测定盐酸雷尼替丁和尼扎替丁原料药中N-亚硝基二甲胺.方法:采用 Phenomenex ACE Excel 3 C18-AR 色谱柱(4.6 mm×100 mm,3 mm),以0.1％甲酸水-0.1％甲酸甲醇为流动相,梯度洗脱,流速0.5 mL·min-1,柱温40℃,紫外检测波长:230 nm,进样量:5μL;质谱离子化方式为APCI,正离子模式,多反应监测(MRM),N-亚硝基二甲胺的定量离子对为m/z 75.0→43.0,定性离子对为m/z 75.0 → 58.0.结果:N-亚硝基二甲胺质量浓度为1～100 ng·mL-1,线性关系良好;检测下限为0.2 ng·mL-1;测定20批样品,N-亚硝基二甲胺的含量为0.03～0.32 μg·g-1.结论:本方法可用于测定盐酸雷尼替丁和尼扎替丁原料药中Nv-亚硝基二甲胺含量.

Two-photon fluorescent Acenaphtho[1,2-b]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN(3)) moieties were combined through an alkyl chain (ANQ-A-M) or a beta-hairpin motif with two aromatic gamma-amino acid residues (ANQ-H-M) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 mu M in the presence of DOPE. However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M/DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M/DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN(3)) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research.

Nitric oxide (NO) is an epoch-making cellular signaling molecule and has been widely recognized as a fundamental participant in many physiological and pathological processes. The development of robust probes for indicating its existence, concentration, and especially the spatiotemporal messages in the subcellular location of live cells is emerging as one of the most intriguing research subjects. In this work, we report the design and synthesis of a new dihydropyridine-derived boron dipyrromethene (BODIPY) sensor (Lyso-DHP) modified with a morpholine unit for sensitively and selectively detecting NO in 100 % aqueous media and lysosomes of living cells. Time/pH-dependent fluorescence experiments in the presence of NO revealed Lyso-DHP was a fast-response probe in an acidic environment. Lyso-DHP showed an ultrahigh “switch-on” ratio (140-fold fluorescence enhancement) and ultralow detection of limit (LoD, 47 nM). Moreover, Lyso-DHP itself and its NO-induced aromatization product Lyso-PY were both cytocompatible. Live-cell-related localization studies including the exogenous/endogenous NO imaging and lysosome targeting demonstrated good cell permeability and feasibility and dependability for application in live cells. The obtained results indicated that Lyso-DHP was capable of tracing subcellular NO with high specificity, precision, and brightness.