First-In-Human Phase I Study of Tinengotinib (TT-00420), a Multiple Kinase Inhibitor, as a Single Agent in Patients With Advanced Solid Tumors.

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy. RESULTS: Forty-eight patients were enrolled (dose escalation, n = 40; dose expansion, n = 8). MTD was not reached; DRDE was 12 mg daily. DLTs were palmar-plantar erythrodysesthesia syndrome (8 mg, n = 1) and hypertension (15 mg, n = 2). The most common treatment-related adverse event was hypertension (50.0%). In 43 response-evaluable patients, 13 (30.2%) achieved partial response (PR; n = 7) or stable disease (SD) ≥ 24 weeks (n = 6), including 4/11 (36.4%) with FGFR2 mutations/fusions and cholangiocarcinoma (PR n = 3; SD ≥ 24 weeks n = 1), 3/3 (100.0%) with hormone receptor (HR)-positive/HER2-negative breast cancer (PR n = 2; SD ≥ 24 weeks n = 1), 2/5 (40.0%) with triple-negative breast cancer (TNBC; PR n = 1; SD ≥ 24 weeks n = 1), and 1/1 (100.0%) with castrate-resistant prostate cancer (CRPC; PR). Four of 12 patients (33.3%; HR-positive/HER2-negative breast cancer, TNBC, prostate cancer, and cholangiocarcinoma) treated at DRDE had PRs. Tinengotinib's half-life was 28-34 hours. CONCLUSIONS: Tinengotinib was well tolerated with favorable pharmacokinetic characteristics. Preliminary findings indicated potential clinical benefit in FGFR inhibitor-refractory cholangiocarcinoma, HER2-negative breast cancer (including TNBC), and CRPC. Continued evaluation of tinengotinib is warranted in phase II trials.

Tumor Mutation Burden-Related Histopathologic Features for Predicting Overall Survival in Gliomas Using Graph Deep Learning.

Tumor mutation burden (TMB) is a potential biomarker for evaluating the prognosis and response to immune checkpoint inhibitors, but its costly and time-consuming method of measurement limits its widespread application. This study aimed to identify the TMB-related histopathologic features from hematoxylin and eosin slides and explore their prognostic value in gliomas. TMB-related features were detected using a graph convolutional neural network from whole-slide images of patients from The Cancer Genome Atlas data set (619 patients), and the correlation between features and TMB was evaluated in an external validation set (237 patients). TMB-related features were used for predicting overall survival (OS) of patients to investigate whether these features have potential for prognostic prediction. Moreover, biological pathways underlying the prognostic value of the features were further explored. Histopathologic features derived from whole-slide images were significantly associated with patient TMB (P = 0.007 in the external validation set). TMB-related features showed excellent performance for OS prediction, and patients with lower-grade gliomas could be further stratified into different risk groups according to the features (P = 0.00013; hazard ratio, 4.004). Pathways involved in the cell cycle and execution of immune response were enriched in patients with higher OS risk. The TMB-related features could be used to estimate TMB and aid in prognostic risk stratification of patients with glioma with dysregulated biological pathways.

Enzyme-Responsive Fluorescent Labeling Strategy for In Vivo Imaging of Gut Bacteria.

Myrosinase (Myr), as a unique ß-thioglucosidase enzyme capable of converting natural and gut bacterial metabolite glucosinolates into bioactive agents, has recently attracted a great deal of attention because of its essential functions in exerting homeostasis dynamics and promoting human health. Such nutraceutical and biomedical significance demands unique and reliable strategies for specific identification of Myr enzymes of gut bacterial origin in living systems, whereas the dearth of methods for bacterial Myr detection and visualization remains a challenging concern. Herein, we present a series of unique molecular probes for specific identification and imaging of Myr-expressing gut bacterial strains. Typically, an artificial glucosinolate with an azide group in aglycone was synthesized and sequentially linked with the probe moieties of versatile channels through simple click conjugation. Upon gut bacterial enzymatic cleavage, the as-prepared probe molecules could be converted into reactive isothiocyanate forms, which can further act as reactive electrophiles for the covalent labeling of gut bacteria, thus realizing their localized fluorescent imaging within a wide range of wavelength channels in live bacterial strains and animal models. Overall, our proposed method presents a novel technology for selective gut bacterial Myr enzyme labeling in vitro and in vivo. We envision that such a rational probe design would serve as a promising solution for chemoprevention assessment, microflora metabolic mechanistic study, and gut bacterium-mediated physiopathological exploration.

Enzymes in Synergy: Bacteria Specific Molecular Probe for Locoregional Imaging of Urinary Tract Infection in vivo.

Uropathogenic Escherichia coli (UPECs) is a leading cause for urinary tract infections (UTI), accounting for 70-90% of community or hospital-acquired bacterial infections owing to high recurrence, imprecision in diagnosis and management, and increasing prevalence of antibiotic resistance. Current methods for clinical UPECs detection still rely on labor-intensive urine cultures that impede rapid and accurate diagnosis for timely UTI therapeutic management. Herein, we developed a first-in-class near-infrared (NIR) UPECs fluorescent probe (NO-AH) capable of specifically targeting UPECs through its collaborative response to bacterial enzymes, enabling locoregional imaging of UTIs both in vitro and in vivo. Our NO-AH probe incorporates a dual protease activatable moiety, which first reacts with OmpT, an endopeptidase abundantly present on outer membrane of UPECs, releasing an intermediate amino acid residue conjugated with a NIR hemicyanine fluorophore. Such liberated fragment would be subsequently recognized by aminopeptidase (APN) within periplasm of UPECs, activating localized fluorescence for precise imaging of UTIs in complex living environments. The peculiar specificity and selectivity of NO-AH, facilitated by the collaborative action of bacterial enzymes, features a timely and accurate identification of UPECs-infected UTIs, which could overcome misdiagnosis in conventional urine tests, thus opening new avenues towards reliable UTI diagnosis and personalized antimicrobial therapy management.

Near Infrared-II Photothermal and Colorimetric Synergistic Sensing for Intelligent Onsite Dietary Myrosinase Profiling.

Myrosinase (Myr) is a type of critical ß-thioglucosidase enzyme activator essential for sustaining many functional foods to perform their health-promoting functions. An accurate and reliable Myr test is meaningful for food quality and dietary nutrition assessments, whereas the currently reported methods do not guarantee specificity and have high reliance on instrumentation, which are not suitable for rapid and onsite Myr screening especially in complex systems from various sources. Herein, we present a unique NIR-II absorption-based photothermal-responsive colorimetric biosensor for anti-interference onsite Myr determination and realization of rapid visualized outputs with the aid of smartphone calculation. Typically, assisted by glucose oxidase (GOx), Myr specifically converts the sinigrin substrate into hydrogen peroxide (H2O2) that can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by AuNPs to form a charge transfer complex (CTC) with NIR-II absorption and photothermal characters. Delightfully, such a proposed method is able to determine Myr within a wide range of 0 to 172.5 mU/mL with a detection limit down to 2.96 mU/mL. Moreover, simple, rapid, and real-time visual Myr identification in actual food-sourced samples could also be readily achieved by smartphone readout processing, with the promising advantages of anti-interference, high accuracy, and low cost as well as labor-saving and intelligence engagement, thus providing great feasibility for precise measurement in complex and dynamic dietary sample analysis. Overall, our proposed method presents a novel technology for onsite dietary Myr enzyme profiling, which is promising to be applied in the food industry for nutritional composition profiles, freshness evaluation, and quality assessment.

NIR-II Ratiometric Lanthanide-Dye Hybrid Nanoprobes Doped Bioscaffolds for In Situ Bone Repair Monitoring.

In situ monitoring of tissue regeneration progression is of primary importance to basic medical research and clinical transformation. Despite significant progress in the field of tissue engineering and regenerative medicine, few technologies have been established to in situ inspect the regenerative process. Here, we present an integrated second near-infrared (NIR-II, 1000-1700 nm) window in vivo imaging strategy based on 3D-printed bioactive glass scaffolds doped with NIR-II ratiometric lanthanide-dye hybrid nanoprobes, allowing for in situ monitoring of the early inflammation, angiogenesis, and implant degradation during mouse skull repair. The functional bioactive glass scaffolds contribute to more effective bone regeneration because of their excellent angiogenic and osteogenic activities. The reliability of ratiometric fluorescence imaging, coupled with low autofluoresence in the NIR-II window, facilitates the accuracy of in vivo inflammation detection and high-resolution visualization of neovascularization and implant degradation in deep tissue.

Molecular Defensive Mechanism of Echinacea purpurea (L.) Moench against PAH Contaminations.

The understanding of the molecular defensive mechanism of Echinacea purpurea (L.) Moench against polycyclic aromatic hydrocarbon (PAH) contamination plays a key role in the further improvement of phytoremediation efficiency. Here, the responses of E. purpurea to a defined mixture of phenanthrene (PHE) and pyrene (PYR) at different concentrations or a natural mixture from an oilfield site with a history of several decades were studied based on transcriptomics sequencing and widely targeted metabolomics approaches. The results showed that upon 60-day PAH exposure, the growth of E. purpurea in terms of biomass (p < 0.01) and leaf area per plant (p < 0.05) was negatively correlated with total PAH concentration and significantly reduced at high PAH level. The majority of genes were switched on and metabolites were accumulated after exposure to PHE + PYR, but a larger set of genes (3964) or metabolites (208) showed a response to a natural PAH mixture in E. purpurea. The expression of genes involved in the pathways, such as chlorophyll cycle and degradation, circadian rhythm, jasmonic acid signaling, and starch and sucrose metabolism, was remarkably regulated, enhancing the ability of E. purpurea to adapt to PAH exposure. Tightly associated with transcriptional regulation, metabolites mainly including sugars and secondary metabolites, especially those produced via the phenylpropanoid pathway, such as coumarins, flavonoids, and their derivatives, were increased to fortify the adaptation of E. purpurea to PAH contamination. These results suggest that E. purpurea has a positive defense mechanism against PAHs, which opens new avenues for the research of phytoremediation mechanism and improvement of phytoremediation efficiency via a mechanism-based strategy.

A hybrid erbium(III)-bacteriochlorin near-infrared probe for multiplexed biomedical imaging.

Spectrally distinct fluorophores are desired for multiplexed bioimaging. In particular, monitoring biological processes in living mammals needs fluorophores that operate in the 'tissue-transparent' near-infrared (NIR) window, that is, between 700 and 1,700 nm. Here we report a fluorophore system based on molecular erbium(III)-bacteriochlorin complexes with large Stokes shift (>750 nm) and narrowband NIR-to-NIR downconversion spectra (full-width at half-maximum ≤ 32 nm). We have found that the fast (2 × 109 s-¹) and near-unity energy transfer from bacteriochlorin triplets to the erbium(III) 4I13/2 level overcomes the notorious vibrational overtones quenching, resulting in bright and long-lived (1.73 µs) 1,530 nm luminescence in water. We demonstrate the excitation/emission-multiplexed capability of the complexes in the visualization of dynamic circulatory and metabolic processes in living mice, and through skull tracking of cancer cell metastases in mouse brain. This hybrid probe system facilitates robust multiplexed NIR imaging with high contrast and spatial resolution for applications ranging from fluorescence-guided surgery, diagnostics and intravital microscopy.

Changes in retinal vascular bifurcation in eyes with myopia.

OBJECTIVE: To evaluate the effect of myopia on retinal vascular bifurcation. METHODS: A cross-sectional study that retrospectively analyzed the fundus photographs and clinical data of 493 people who participated in routine physical examinations in Huadong Sanatorium. One eye of each subject was included in the analysis. Retinal vascular bifurcation measurements were extracted by using a validated computer program. One-way ANOVA and analysis of covariance were performed to compare the measurements across high myopia, low to moderate myopia, and non-myopia groups. RESULTS: The mean age was 41.83 ± 10.43 years and 63.49% were women. The mean spherical equivalent refraction (SER) was - 4.59 ± 3.07 D. Ninety-nine (20.08%) eyes met the definition of high myopia (SER ≤ -6.0 D), along with 234 (47.46%) low to moderate myopia (-6.0 D < SER <-0.5 D), and 160 (32.45%) non-myopia (SER ≥ -0.5 D). The differences in the arteriolar branching angle, venular branching coefficient, venular asymmetry ratio, venular angular asymmetry, and venular junctional exponent among the three groups remained significant (p < 0.05) after multivariate adjustment. Pairwise comparisons showed arteriolar branching angle and venular angular asymmetry in high myopia were significantly lower than low to moderate myopia (p < 0.001, p = 0.014 respectively) and non-myopia (p = 0.007, p = 0.048 respectively). Venular asymmetry ratio and venular branching coefficient in high myopia were significantly higher than low to moderate myopia (p = 0.029, p = 0.001 respectively) and non-myopia (p = 0.041, p = 0.043 respectively). There was a significant difference in venular junctional exponent between high myopia and low to moderate myopia (p = 0.031). CONCLUSION: The vascular bifurcation differs in dependence on the myopic refractive error and a significant increase in the difference can be observed in high myopic eyes.

Metal and Metal Oxide Nanomaterials for Fighting Planktonic Bacteria and Biofilms: A Review Emphasizing on Mechanistic Aspects.

The misuse and mismanagement of antibiotics have made the treatment of bacterial infections a challenge. This challenge is magnified when bacteria form biofilms, which can increase bacterial resistance up to 1000 times. It is desirable to develop anti-infective materials with antibacterial activity and no resistance to drugs. With the rapid development of nanotechnology, anti-infective strategies based on metal and metal oxide nanomaterials have been widely used in antibacterial and antibiofilm treatments. Here, this review expounds on the state-of-the-art applications of metal and metal oxide nanomaterials in bacterial infective diseases. A specific attention is given to the antibacterial mechanisms of metal and metal oxide nanomaterials, including disrupting cell membranes, damaging proteins, and nucleic acid. Moreover, a practical antibiofilm mechanism employing these metal and metal oxide nanomaterials is also introduced based on the composition of biofilm, including extracellular polymeric substance, quorum sensing, and bacteria. Finally, current challenges and future perspectives of metal and metal oxide nanomaterials in the anti-infective field are presented to facilitate their development and use.

Development and validation of a machine learning algorithm-based risk prediction model of pressure injury in the intensive care unit.

The study aimed to establish a machine learning-based scoring nomogram for early recognition of likely pressure injuries in an intensive care unit (ICU) using large-scale clinical data. A retrospective cohort study design was employed to develop and validate a top-performing clinical feature panel accessibly in the electronic medical records (EMRs), which was in the mode of a quantifiable nomogram. Clinical factors regarding demographics, admission cause, clinical laboratory index, medical history and nursing scales were extracted as risk candidates. The performance improvement was based on the application of the machine learning technique, comprising logistic regression, decision tree and random forest algorithm with five-fold cross-validation (CV) technique. The comprehensive assessment of sensitivity, specificity and the area under the receiver operating characteristic curve (AUROC) was considered in the evaluation of predictive performance. The receiver operating characteristic curves revealed the top performance for the logistic regression model in respect to machine learning improvement, achieving the highest sensitivity and AUC among three types of classifiers. Compared against the 23-point Braden scale routinely recorded online, an incorporated nomogram of logistic regression model and Braden scale achieved the best performance with an AUC of 0.87 ± 0.07 and 0.84 ± 0.05 in training and test cohort, respectively. Our findings suggest that the machine learning technique potentiated the limited predictive validity of routinely recorded clinical data on pressure injury development during ICU hospitalisation. Easily accessible electronic records held the potentials to substitute the traditional Braden score in the prediction of pressure injury in intensive care unit. Preoperative prediction of pressure injury facilitates the exemption from the severe consequences.

Counterion-Paired Bright Heptamethine Fluorophores with NIR-II Excitation and Emission Enable Multiplexed Biomedical Imaging.

Photon excitation and emission at the NIR-II spectral window enable high-contrast deep-tissue bioimaging. However, multiplexed imaging with NIR-II excitation and emission has been hampered by the limited chemical strategies to develop bright fluorophores with tunable absorption in this spectral regime. Herein, we developed a series of heptamethine cyanines (HCs) with varied absorption/emission maxima spanning from 1100 to 1600 nm through a physical organic approach. A bulky counterion paired to HCs was found to elicit substantial improvements in absorptivity (7-fold), brightness (14-fold), and spectral profiles in water, addressing a notorious quenching problem of NIR-II cyanines due to aggregation and polarization. We demonstrated the utilities of HC1222 and HC1342 for high-contrast dual-color imaging of circulatory system, lymphatic structures, tumor, and organ function in living mice under 1120 nm and 1319 nm excitation, showing HCs as a promising platform for non-invasive bioimaging.

Stable Monodisperse Pb1-x Cdx S Quantum Dots for NIR-II Bioimaging by Aqueous Coprecipitation of Bimetallic Clusters.

Aqueous lead sulfide (PbS) quantum dots (QDs) synthesized by traditional methods are unstable, so that they are usually coated with cadmium sulfide (CdS) to prevent oxidation, which are complicated and not satisfactory for mass production. Here, stable ternary Pb1-x Cdx S QDs were synthesized by in situ coprecipitation of Pb4-n Cdn O4 bimetallic clusters in an aqueous solution, which possess a uniform size of 4.0±0.2 nm and the second near-infrared (NIR-II) emission at 1100 nm with photoluminescence quantum yield (PLQY) as high as 17.72 %. Stored at 4 °C and in colloidal form, the PLQY of Pb1-x Cdx S QDs remained at 90.9 % of the initial value after 15 days, while stored as powder, the spectra did not change after 5 months. The high PLQY and good water compatibility of Pb1-x Cdx S QDs provide a good performance in vivo vasculature imaging and lymphatic system imaging at a very low power density (10 mW cm-2 ) in the NIR-II window.

Bright and Stable NIR-II J-Aggregated AIE Dibodipy-Based Fluorescent Probe for Dynamic In†Vivo Bioimaging.

Organic dyes emitting in the second near-infrared (NIR-II, 900-1700 nm) window, with high molar extinction coefficients (MEC) and quantum yields (QY) in aqueous, are essential for in vivo bioimaging and biosensing. In this work, we developed a dibodipy-based aggregation-induced emission (AIE) fluorescent probe, THPP, to meet this aim. THPP exhibits a high MEC and has intensified absorption and emission in J-aggregated state, which significantly enhance the fluorescence intensity (≈55 folds) and extend the maximal absorption/emission wavelengths to 970/1010 nm in NIR-II region. Based on the bright THPP, imaging with a high frame rate (34 frames per second) at a deep "valid penetration depth" up to 6 mm can be achieved. This enabled simultaneous and dynamic imaging of vasculatures and deep tissues. Besides, we succeeded in monitoring the respiratory rate of acute-lung-injury mice and tracing the collateral circulation process with a high frame rate.

High-Fidelity NIR-II Multiplexed Lifetime Bioimaging with Bright Double Interfaced Lanthanide Nanoparticles.

Fluorescence lifetime imaging provides more possibility of in vivo multiplexing in second near infrared (NIR-II) window. However, it still faces the obstacle that fluorescent probes with differentiable lifetime often exhibit quite different fluorescence intensity, especially the short lifetime usually accompanies with a weak fluorescence intensity, resulting in the difficulty for simultaneously decoding multiplexed lifetime information due to the interference of background noise. To facilitate high-fidelity lifetime multiplexed imaging, we developed a series of Er3+ doped double interface fluorescent nanoprobes (Er-DINPs): α-NaYF4 @NaErF4 : Ce@NaYbF4 @NaErF4 : Ce@NaYF4 with strong fluorescence intensity and easily distinguishable fluorescence lifetime. Both in vitro and in vivo experimental results confirmed the advantage of these probes with comparable fluorescence intensity for high-fidelity multiplexed lifetime bioimaging.

An Aqueous Route Synthesis of Transition-Metal-Ions-Doped Quantum Dots by Bimetallic Cluster Building Blocks.

Water-soluble doped quantum dots have unique photophysical properties and functionalities as optical labels for bioimaging and chemo-/biosensing. However, doping in quantum dots is not easy due to the dopant-ion size mismatch and "self-purification" effect. Here, we demonstrate a successful preparation of Mn-, Cu-, and Ni-doped CdS quantum dots with bimetallic clusters instead of ions as building blocks under mild aqueous conditions up to gram scale. The representative Mn-doped quantum dots have uniform size, about 3.2 ± 0.5 nm, and emit at 620 nm. The doping concentration can be adjusted in the range 6.4%-25.7%. On the premise of good water solubility, they are stable and nontoxic so as to be directly used for cell imaging. Copper and nickel doping have similar results. Because of the close sizes of bimetallic clusters and the low reaction temperature, the challenges posed by dopant size mismatch and ion diffusion are ignored. X-ray absorption fine structure analysis proves that dopants are inside the quantum dots rather than on the surface, indicating that the "self-purification" effect can be effectively overcome. Furthermore, codoped ZnS quantum dots with adjustable emission are achieved, which validates the versatility of our new approach.

Surface-Confined Winding Assembly of Mesoporous Nanorods.

Bending and folding are important stereoscopic geometry parameters of one-dimensional (1D) nanomaterials, yet the precise control of them has remained a great challenge. Herein, a surface-confined winding assembly strategy is demonstrated to regulate the stereoscopic architecture of uniform 1D mesoporous SiO2 (mSiO2) nanorods. Based on this brand-new strategy, the 1D mSiO2 nanorods can wind on the surface of 3D premade nanoparticles (sphere, cube, hexagon disk, spindle, rod, etc.) and inherit their surface topological structures. Therefore, the mSiO2 nanorods with a diameter of ∼50 nm and a variable length can be bent into arc shapes with variable radii and radians, as well as folded into 60, 90, 120, and 180° angular convex corners with controllable folding times. Additionally, in contrast to conventional core@shell structures, this winding structure induces partial exposure and accessibility of the premade nanoparticles. The functional nanoparticles can exhibit large accessible surface and efficient energy exchanges with the surroundings. As a proof of concept, winding-structured CuS&mSiO2 nanocomposites are fabricated, which are made up of a 100 nm CuS nanosphere and the 1D mSiO2 nanorods with a diameter of ∼50 nm winding the nanosphere in the perimeter. The winding structured nanocomposites are demonstrated to have fourfold photoacoustic imaging intensity compared with the conventional core@shell nanostructure with an inaccessible core because of the greatly enhanced photothermal conversion efficiency (increased by ∼30%). Overall, our work paves the way to the design and synthesis of 1D nanomaterials with controllable bending and folding, as well as the formation of high-performance complex nanocomposites.

MicroRNA-621 inhibits the growth of gastric cancer cells by targeting SYF2.

Increasing evidence indicates that aberrantly expressed microRNAs play a role in tumorigenesis and progression of gastric cancer. Recently, a novel cancer-related microRNA, miR-621, was found to be involved in cancer pathogenesis. However, the precise molecular mechanisms underlying the oncogenic activity of miR-621 remain unclear and require further investigation. In the current study, we demonstrate that miR-621 expression is downregulated in gastric cancer tissues and cell lines, and its reduction is associated with malignant clinical features including tumor size, lymph node metastasis, tumor-node-metastasis stage and poor prognosis. Functional studies involving gain- and loss-of-function experiments revealed that miR-621 represses cell viability, colony formation, cell cycle progression and proliferation in vitro, and miR-621 overexpression inhibited tumor growth in a gastric cancer xenograft model. SYF2 was identified as a direct target gene of miR-621 in gastric cancer. MiR-621 directly interacts with the SYF2 3'-UTR and post-transcriptionally repressed SYF2 expression in gastric cancer cells. SYF2 was significantly overexpressed in gastric cancer tissues and negatively correlated with miR-621 expression. Moreover, inhibition of SYF2 expression reversed the effects of miR-621 loss in gastric cancer cells. SYF2 overexpression was similar to that induced by miR-621 loss in gastric cancer. Taken together, these studies suggest that miR-621 may be a viable therapeutic target in gastric cancer.

Isolation and Identification of Three New Sterigmatocystin Derivatives from the Fungus Aspergillus versicolor Guided by Molecular Networking Approach.

Molecular networking approach was applied for the targeted isolation of new sterigmatocystin derivatives, sterigmatocystins A-C, from the marine sponge-derived fungus Aspergillus versicolor. Sterigmatocystin A features a rare 6/6/6/6/5 polycyclic system. The structures of sterigmatocystins A-C, including absolute configurations, were determined on the basis of spectroscopic data and ECD calculations. Sterigmatocystin A showed more stronger promoting angiogenesis activity than the positive control at 1.25 µM level in transgenic fluorescent zebrafish. Sterigmatocystins A-C also exhibited moderate antiviral activity by the inhibition of HSV-2.

J-Aggregates of Cyanine Dye for NIR-II in Vivo Dynamic Vascular Imaging beyond 1500 nm.

Light in the second near-infrared window, especially beyond 1500 nm, shows enhanced tissue transparency for high-resolution in vivo optical bioimaging due to decreased tissue scattering, absorption, and autofluorescence. Despite some inorganic luminescent nanoparticles have been developed to improve the bioimaging around 1500 nm, it is still a great challenge to synthesize organic molecules with the absorption and emission toward this region. Here, we present J-aggregates with 1360 nm absorption and 1370 nm emission formed by self-assembly of amphiphilic cyanine dye FD-1080 and 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Molecular dynamics simulations were further employed to illustrate the self-assembly process. Superior spatial resolution and high signal-to-background ratio of J-aggregates were demonstrated for noninvasive brain and hindlimb vasculature bioimaging beyond 1500 nm. The efficacy evaluation of the clinically used hypotensor is successfully achieved by high-resolution in vivo dynamic vascular imaging with J-aggregates.