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Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria; a positively charged component that targets the drug beacon to mitochondria; and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation. Drug beacon CHB inhibits energy production by binding to ATP/ADP in mitochondria, disrupting the structure and function of mitochondria, exerting anti-tumor effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a second messenger playing crucial roles in the signaling of a variety of cellular functions. Due to its pathophysiological significance, various NO modulators have been developed to explore NO pathways and some have been used as therapies. These modulators are often used directly to observe pharmacological effects in cell lines, but their actual effect on intracellular NO level is seldom analyzed. Herein, facilitated by a selective and sensitive fluorescence probe, we observed that some NO modulators displayed unexpected behaviors with both NO scavenger carboxy-PTIO and endothelial nitric oxide synthase (eNOS) inhibitor N(ω)-nitro- l -arginine methyl ester (l -NAME) failing to decrease intracellular free NO level in EA. hy926 cells while NO donor diethylamine-NONOate (DEA·NONOate) and eNOS activator calcimycin (A23187) failing to increase free NO level in human umbilical vein endothelial cell line (HUV-EC-C), although the reagents were confirmed to work normally in the primary human umbilical vein endothelial cells (primary HUVECs) and RAW 264.7 macrophage cells. Further research suggested that these unusual behaviors might be attributed to the cellular microenvironments including both the NO synthase (NOS) level and the endogenous glutathione (GSH) level. Genetically manipulating eNOS level in both cells restores the expected response, while decreasing GSH level restores the ability of DEA·NONOate to increase NO level in HUV-EC-C. These results reveal that the cellular microenvironment has a profound impact on pharmacological effect. Our study suggests GSH as a reservoir for NO in live cells and highlights the value of chemical probes as valuable tools to reveal microenvironment-dependent pharmacological effects. Image 1 • An imaging based method for evaluating the efficacy of NO modulators in live cells was developed. • Some NO modulators were observed yielding unexpected effects on cellular NO levels in some endothelial cell lines. • Further study unveiled intracellular microenvironments have profound effects on the efficacy of NO modulators in live cells. • This result highlights the pitfall of the specific cellular microenvironments on drug efficacy. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional imaging modalities for optically dense connective tissues such as tendons are limited and typically have a single imaging methodological endpoint. Here, we have developed a bimodal procedure utilising fluorescence-based confocal microscopy and x-ray micro-computed tomography for the imaging of adult tendons to visualise and analyse extracellular sub-structure and cellular composition in small and large animal species. Results: Using fluorescent immunolabelling and optical clearing, we visualised the expression of the novel cross-species marker of tendon basement membrane, laminin-α4 in 3D throughout whole rat Achilles tendons and equine superficial digital flexor tendon 5 mm segments. This revealed a complex network of laminin-α4 within the tendon core that predominantly localises to the interfascicular matrix compartment. Furthermore, we implemented a chemical drying process capable of creating contrast densities enabling visualisation and quantification of both fascicular and interfascicular matrix volume and thickness by x-ray micro-computed tomography. We also demonstrated that both modalities can be combined using reverse clarification of fluorescently labelled tissues prior to chemical drying to enable bimodal imaging of a single sample. Conclusions: Whole-mount imaging of tendon allowed us to identify the presence of an extensive network of laminin-α4 within tendon, the complexity of which cannot be appreciated using traditional 2D imaging techniques. Creating contrast for x-ray micro-computed tomography imaging of tendon using chemical drying is not only simple and rapid, but also markedly improves on previously published methods. Combining these methods provides the ability to gain spatio-temporal information and quantify tendon substructures to elucidate the relationship between morphology and function. [ABSTRACT FROM AUTHOR]

Background: Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. ABPP utilizes cell/tissue proteomes and features the FP-warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Existing ABPP approaches characterize global SH activity based on mobility in gel or MS-based target identification and cannot reveal the identity of the cell-type responsible for an individual SH activity originating from complex proteomes. Results: Here, by using an activity probe with broad reactivity towards the SH family, we advance the ABPP methodology to glioma brain cryosections, enabling for the first time high-resolution confocal fluorescence imaging of global SH activity in the tumor microenvironment. Tumor-associated cell types were identified by extensive immunohistochemistry on activity probe-labeled sections. Tissue-ABPP indicated heightened SH activity in glioma vs. normal brain and unveiled activity hotspots originating from tumor-associated neutrophils (TANs), rather than tumor-associated macrophages (TAMs). Thorough optimization and validation was provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Conclusions: Our study advances the ABPP methodology to tissue sections, enabling high-resolution confocal fluorescence imaging of global SH activity in anatomically preserved complex native cellular environment. To achieve global portrait of SH activity throughout the section, a probe with broad reactivity towards the SH family members was employed. As ABPP requires no a priori knowledge of the identity of the target, we envisage no imaginable reason why the presently described approach would not work for sections regardless of species and tissue source. [ABSTRACT FROM AUTHOR]

Highlights • Fabrication of fluorescent nanodiamonds through a one-step thiol-ene click reaction. • These FNDs show excellent physicochemical properties. • These FNDs would potentially utilized for biological imaging and drug delivery. • This method should also be adopted for preparation of other FNDs. Abstract Fluorescent nanodiamonds (FNDs) have attracted wide research interest due to their excellent optical properties and outstanding biocompatibility. Nevertheless, the complex preparation methods and high costs of FNDs still perplex their further biomedical applications. In this contribution, we developed an efficient one-step method for the preparation of water dispersible FNDs through a thiol-ene click reaction for the first time. Furthermore, a mass of carboxylic groups are introduced on the surface of FNDs, and this mass could lead to the dispersibility of FNDs in aqueous solutions. More importantly, the carboxylic groups on the surface of FNDs could further conjugate with various drug molecules and macromolecules. Therefore, the facile strategy for the preparation of FNDs with unique characteristics via the one-step thiol-ene reaction is expected to have high potential for various biomedical applications. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

This study was performed to optimize scan delays for canine kidney by using a bolus-tracking technique. In six beagle dogs, computed tomography (CT) of the kidney was performed three times in each dog with different scan delays after a bolus-tracking trigger of 100 Hounsfield units (HU) of aortic enhancement. Delays were 5, 20, 35, and 50 sec for the first scan, 10, 25, 40, and 55 sec for the second scan, and 15, 30, 45, and 60 sec for the third scan. The renal artery-to-vein contrast difference peaked at 5 sec, and the renal cortex-to-medulla contrast difference peaked at 10 sec. The renal cortex-to-medulla contrast difference approached zero at a scan delay of 30 sec after the bolus trigger. For the injection protocol used in this study, the optimal scan delay times for renal arterial, corticomedullary, and nephrographic phases were 5, 10, and 30 sec after triggering at 100 HU of aortic enhancement using the bolus-tracking technique. The bolus-tracking technique is useful in multi-phase renal CT study as it compensates for different transit times to the kidney among different animals, requires a small dose of contrast media, and does not require additional patient radiation exposure. [ABSTRACT FROM AUTHOR]

Supramolecular interactions between individual molecules are universal forces in living organisms and have been extensively investigated and utilized for fabrication of multifunctional materials over the past few decades. In this work, we reported a rather facile strategy to fabricate the fluorescent organic nanoparticles (FONs) with red fluorescence and aggregation-induced emission (AIE) feature through the supramolecular interactions between the β cyclodextrin (β-CD) and adamantine terminating AIE dye. The structures of prepared Ph-Ad/β-CD FONs were characterized by 1 H nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) spectroscopy. The size and morphology of the final self-assemblies (named as Ph-Ad/β-CD FONs) was characterized by transmission electronic microscopy (TEM). Results demonstrated that these AIE-active FONs can self-assemble into nanoparticles with excellent dispersity and strong fluorescence due to their AIE feature. Biological evaluation demonstrated that Ph-Ad/β-CD FONs has superior biocompatibility and imaging performance. These features endow the Ph-Ad/β-CD FONs good performance in biomedical fields. [ABSTRACT FROM AUTHOR]

Fluorescence imaging in the second near-infrared (NIR-II) window is well suited for biological systems due to lower tissue scattering and micrometer-scale resolution at depths of millimeters. Unfortunately, none of the NIR-II fluorophores have clinical application due to low quantum yields, poor photostability, and long-term biosafety concerns. Herein, we develop NIR-II fluorescent nanoprobes based on the "isolated cage" monodisperse strategy, which significantly inhibits the π-π stacking interactions and restricts internal rotation of the arrested indocyanine green (ICG) fluorophores, which minimizes aggregation-caused quenching and enhances their NIR-II imaging performance. Unlike ICG's imaging window of several minutes, the nanoformulations have reduced photobleaching and provide longer observation times. The increased imaging time allows high spatiotemporal resolution of blood vessels and lymphatic system. Benefiting from the high resolution and sensitivity of the nanoprobes, sentinel lymph nodes are accurately removed under fluorescence navigation. More intriguingly, the patency of lymphovenous anastomosis (LVA) is presented more intuitively by qualitative and quantitative NIR-II fluorescence signals, which will directly benefit the innovation and promotion of LVA. [Display omitted] • PCMI NPs are developed based on the "isolated cage" monodisperse strategy, which significantly minimizes aggregation-caused quenching of ICG fluorophores and enhances their NIR-II imaging performance. • PCMI NPs could afford high spatiotemporal resolution of blood vessels and lymphatic system imaging in vivo. • The patency of lymphovenous anastomosis (LVA) is presented more intuitively by qualitative and quantitative NIR-II fluorescence signals of PCMI NPs. [ABSTRACT FROM AUTHOR]

Fluorescent-intraoperative navigation is a visual technique that allows surgeons to accurately distinguish malignant and normal tissues during surgery. It has the advantages of immediacy, high resolution, and high specificity. However, a single fluorescent source cannot provide sufficient surgical information. Multicolour carbon dots (CDs) are more suitable since they provide outstanding water solubility, photostability, and multicolour-fluorescence imaging. Here, we prepared an optical probe with CD-based multicolour-fluorescence imaging via a hydrothermal method. CDs can be endocytosed by tumour cells, and after intravenous injection, they can effectively accumulate at the tumour site. In a pancreatic cancer mouse model, we demonstrated the multicolour-fluorescence imaging capabilities of CDs, which aided the accurate resection of tumours under fluorescent-intraoperative navigation. Stereoscopic fluorescence microscopy imaging and H&E staining proved that the removed tissue belonged to the pancreatic tumour. This study emphasizes the potential of CDs for fluorescence-guided intraoperative resection and expands the application of CDs in biological fields. an optical probe with CD-based multicolour fluorescence imaging was successfully prepared, via a hydrothermal method. In orthotopic pancreatic cancer mouse model, the probe can efficiently accumulate at the tumour site through intravenous injection. At different wavelengths, the tumour margin was accurately identified and the tumour infiltration depth was shown. [Display omitted] [ABSTRACT FROM AUTHOR]

Multifunctional nanoparticles which integrate the therapeutic agents and bio-imaging agents into one carrier are emerging as a promising therapeutic platform. Herein, GaOOH:Cr 3+ was firstly synthesized using improved hydrothermal method (atmospheric pressure, 95 °C), and by manipulating the pH of the reaction medium, GaOOH:Cr 3+ with different sizes (125.70 nm, 200.60 nm and 313.90 nm) were synthesized. Then β-Ga 2 O 3 :Cr 3+ nanoparticles with porous structures were developed as a result of the calcination of GaOOH:Cr 3+ . The fabricated, porous β-Ga 2 O 3 :Cr 3+ nanoparticles could effectively absorb doxorubicin hydrochloride (DOX) (loading rate: 8% approximately) and had near infrared photoluminescence with a 695 nm emission. Furthermore, β-Ga 2 O 3 :Cr 3+ nanoparticles were coated with l -Cys modified hyaluronic acid (HA-Cys) by exploiting the electrostatic interaction and the cross-link effect of disulfide bond to improve the stability. The DOX loaded HA-Cys coated β-Ga 2 O 3 :Cr 3+ nanoparticles (HA/β-Ga 2 O 3 :Cr 3+ /DOX) showed an oxidation–reduction sensitive drug release behavior. The HA-Cys coated β-Ga 2 O 3 :Cr 3+ nanoparticles showed a low cytotoxicity on MCF-7 and Hela cell lines. The cellular uptake of HA/β-Ga 2 O 3 :Cr 3+ /DOX using the near infrared photoluminescence of β-Ga 2 O 3 :Cr 3+ nanoparticles and the fluorescence of DOX demonstrated the HA/β-Ga 2 O 3 :Cr 3+ /DOX could internalize into tumor cells quickly, which was affected by the size and shape of β-Ga 2 O 3 :Cr 3+ nanoparticles. [ABSTRACT FROM AUTHOR]

Despite the ancient discovery of the basic physical phenomenon underlying optoacoustic imaging and tomography [1], the lack of suitable laser sources, ultrasound detection technology, data acquisition, and processing capacities has long hindered the realization of efficient imaging devices. In fact, the first high-quality images from living animals were obtained about a decade ago (Figure 1), which was followed by an exponential growth of technical developments in instrumentation, algorithms, and biomedical applications surrounding this fascinating field. The ability of optoacoustics to probe optical contrast along a wide domain of penetration scales while maintaining excellent spatiotemporal resolution representative of ultrasound imaging, as shown in Figure 2, is unparalleled among the other optical imaging modalities [2], [3]. [ABSTRACT FROM PUBLISHER]

On a video screen, against a black backdrop, 15 spherical blue-green cells vibrate with a quiet energy. Slowly at first, then faster, they begin to roil and roll. Within the confines of their round membrane cases, they divide, becoming two, three, four cells, then those, in turn, divide to become eight. One splits into two, then pauses, struggling to catch up and spinning off pieces of cellular detritus as it does. Near the top, another, by now many cells rich, hollows out and expands, contracts, expands, contracts. It falls in upon itself and then hatches, pouring out from its shell and ballooning to the side. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Solution-based development of III–V quantum dots. [•] Case study of In-based and Ga-based quantum dots. [•] A summary of solution-based synthetic approaches. [•] Detailed investigation of key factors for high-quality quantum dots. [•] Excellent performances of III–V quantum dots in several applications. [ABSTRACT FROM AUTHOR]

Abstract: Luminescent functionalized mesoporous SiO2@Eu(OH)3 core-shell microspheres (LFMCSMs) were prepared by coating of europium hydroxide (Eu(OH)3) shell on mesoporous silica (SiO2) nanospheres via a facile one-pot process at low temperature. The FETEM images revealed that a well-defined luminescent europium hydroxide shell was successfully grafted on the surface of mesoporous silica nanospheres. These experimental results showed that the LFMCSM has a typical diameter of ca. 392nm consisting of the silica core with about 230nm in diameter and europium hydroxide shell with an average thickness of about 162nm. LFMCSMs exhibited strong red emission peak upon irradiation with ultraviolet light, which originated from the electric-dipole transition 5D0 → 7F2 (614nm) of Eu3+ ion. The biocompatibility of the synthesized LFMCSMs was evaluated in vitro by assessing their cytotoxic and genotoxic effect on human hepatoblastoma (HepG2) cells using MTT, TUNEL, fluorescent staining, DNA ladder and Gene expression assays respectively. From the Clinical Editor: This paper describes the development of a one-pot synthesis of luminescent mesoporous SiO2@Eu(OH)3 core-shell microspheres and evaluates their favorable in vitro cyto-toxicity and geno-toxicity, and their applications in bio-imaging of these particles that emit bright red signal under UV exposure. [Copyright &y& Elsevier]

Photoluminescent semiconductor quantum dots (QDs) are of significant interest for bioimaging and fluorescence labelling. In this regard, the design and synthesis using a chemical hydrolysis approach is described of high sensitivity and high specificity non-toxic ZnO QDs (∼5 nm). The ZnO QDs, with long term stability of up to 12 months, exhibited strong green yellow emission on doping with small concentration of manganese, which is tunable to the near infrared biological window (about 650-770 nm). Furthermore, the embedding of ZnO QDs on silica nanospheres led to a significant increase in photoluminescence intensity rendering them suitable for bright QD based probes. [ABSTRACT FROM AUTHOR]

Abstract: High-energy proton microscopy provides unique capabilities in penetrating radiography including the combination of high spatial resolution and field-of-view, dynamic range of density for measurements, and reconstructing density variations to less than 1% inside volumes and in situ environments. We have recently proposed to exploit this novel proton radiography technique for image-guided stereotactic particle radiosurgery. Results of a first test for imaging biological and tissue-equivalent targets with high-energy (800 MeV) proton microscopy are presented here. Although we used a proton microscope setup at ITEP (Moscow, Russia) optimized for fast dynamic experiments in material research, we could reach a spatial resolution of 150 μm with approximately 1010 protons per image. The potential of obtaining high-resolution online imaging of the target using a therapeutic proton beam in the GeV energy region suggests that high-energy proton microscopy may be used for image-guided proton radiosurgery. [Copyright &y& Elsevier]

Abstract: The aim of this study was to validate the automatic tracking of facial landmarks in 3D image sequences. 32 subjects (16 males and 16 females) aged 18–35 years were recruited. 23 anthropometric landmarks were marked on the face of each subject with non-permanent ink using a 0.5mm pen. The subjects were asked to perform three facial animations (maximal smile, lip purse and cheek puff) from rest position. Each animation was captured by the 3D imaging system. A single operator manually digitised the landmarks on the 3D facial models and their locations were compared with those of the automatically tracked ones. To investigate the accuracy of manual digitisation, the operator re-digitised the same set of 3D images of 10 subjects (5 male and 5 female) at 1 month interval. The discrepancies in x, y and z coordinates between the 3D position of the manual digitised landmarks and that of the automatic tracked facial landmarks were within 0.17mm. The mean distance between the manually digitised and the automatically tracked landmarks using the tracking software was within 0.55mm. The automatic tracking of facial landmarks demonstrated satisfactory accuracy which would facilitate the analysis of the dynamic motion during facial animations. [Copyright &y& Elsevier]

Wing hearts are small pumping organs that maintain the flow of hemolymph through the wing veins of insects. In Drosophila, these organs consist of parallel oriented muscle cells and a simple epithelium of connective tissue. Both tissues originate from eight embryonic wing heart progenitors (WHPs), which remain dormant until late larval stages. Most of the differentiation and maturation takes place during the pupal stage following head eversion. In this study, we have used the tissue specific expression of Gal4 enhancer lines, in combination with the live cell markers GFP and DsRed to investigate pupal wing heart development in conjunction with the surrounding tissues. We found that WHPs interact with the tracheal system and specific expression domains of the adult epidermis. Additionally, wing heart development occurs simultaneously with the remodeling of the dorso-lateral epidermis into the scutellum and the scutellar arms. Myogenesis in wing hearts comprises known processes such as founder cell specification, but also new features like removal of growing myotubes, and nuclei movement. Wing heart epithelium development is accomplished by the mesenchymal-epithelial transition of WHPs and occurs slightly delayed to muscle development. The epithelium represents a novel mesodermally derived secondary epithelium. Moreover, we have identified a nerve that runs along the epithelium and innervates the wing heart muscle cells. [ABSTRACT FROM AUTHOR]

The article offers information on a study related to labeling of polyethylenimine with fluorescent dye for visualizing the nucleus in digitonin-permeabilized HeLa cells. It informs about the visualization of nucleus of digitonin-permeabilized cervical cancer HeLa cells by its exposure to fluoresceinisothiocyanate-labeled polyethylenimine for diagnosis of cancer.

Abstract: New generation fluorophores, also termed upconversion nanoparticles (UCNPs), have the ability to convert near infrared radiations with lower energy into visible radiations with higher energy via a nonlinear optical process. Recently, these UCNPs have evolved as alternative fluorescent labels to traditional fluorophores, showing great potential for imaging and biodetection assays in both in vitro and in vivo applications. UCNPs exhibit unique luminescent properties, including high penetration depth into tissues, low background signals, large Stokes shifts, sharp emission bands, and high resistance to photobleaching, making UCNPs an attractive alternative source for overcoming current limitations in traditional fluorescent probes. In this article, we discuss the recent progress in the synthesis and surface modification of rare-earth doped UCNPs with a specific focus on their biological applications. From the Clinical Editor: Upconversion nanoparticles – a new generation of fluorophores - convert near infrared radiations into visible radiations via a nonlinear optical process. These UCNPs have evolved as alternative fluorescent labels with great potential for imaging and biodetection assays in both in vitro and in vivo applications. [Copyright &y& Elsevier]

Abstract: Introduction: This study was carried out in cardiology department, Zagazig University from August 2005 to December 2006. This study included 60 patients with first acute anterior myocardial infarction. These patients were 36 male (72%) and 14 female (28%). Aim of the work: The aim of this study is to determine whether early assessment of mitral annular velocities by pulsed wave tissue Doppler imaging predicts left ventricular thrombus formation after first acute anterior myocardial infarction or not. Patients and methods: Patients included in our study represented by first time anterior wall acute myocardial infarction who met the following criteria; chest pain lasting more than 30min, ST segment elevation greater than 2mm in two consecutive anterior electrographic leads and transient elevation of biochemical cardiac markers. Patients were excluded if they had evidence of previous anterior myocardial infarction, valvular heart disease, patients with poor Echo window and conduction abnormalities. All patients were subjected to the following: complete history taking, thorough physical examination, laboratory tests, 12-lead surface ECG, determination if the patient was received thrombolytic therapy or not and echocardiographic evaluation (M-mode, two-dimensional and DTI assessment) was performed for all patients within 24h of arrival to CCU to evaluate LV function and to measure mitral annular velocities then two-dimensional echocardiography to determine thrombus was formed on days 7 and 30. Patients were divided into two groups: group (1); patients with LV thrombus (19 patients “31.6%”) and group (2); patients without LV thrombus (41 patients “68.4%”). Results: There was no significant difference between the two groups as regards age, gender, diabetes mellitus, hypertension, heart rate, peak CPK and whether patients received thrombolytic therapy or not. LVESV and LVEDV were higher in group (1) than in group (2) while EF was lower in group (1) than in group (2). As regards WMSI is higher in group (1) than in group (2). E wave velocity was higher in group (1) than in group (2), while A wave velocity was lower in group (1) than in group (2) and E/A ratio is higher in group (1) than in group (2). Deceleration time of E wave was shorter in group (1) than in group (2) and IVRT were lower in group (1) than in group (2). Em wave velocity was lower in group (1) than in group (2), Am wave velocity had no significant difference between the two groups while Em/Am ratio was lower in group (1) than in group (2) and E/Em ratio was higher in group (1) than in group (2). Sm wave velocity was lower in group (1) than in group (2). From previous data and correlation of TDE finding with other echocardiographic data, we found that systolic and diastolic functions were impaired in patients of group (1) than in group (2) but Sm velocity and WMSI had higher sensitivity and higher specificity (94.7% sensitivity, 95.1% specificity for Sm wave velocity and 94.2% sensitivity, 90.2% specificity for WMSI). Conclusion: From our study, we can conclude that TDE can be used for estimation of systolic and diastolic functions of LV and hence identification of patients at high risk for LV thrombus formation after first time acute anterior myocardial infarction and we recommend more studies to support our results about the importance of the role of oral anticoagulant after AMI. [Copyright &y& Elsevier]

Abstract: Recent advances in nanotechnology have given rise to a new class of fluorescent labels, fluorescent metal nanoclusters, e.g., Au and Ag. These nanoclusters are of significant interest because they provide the missing link between atomic and nanoparticle behavior in metals. Composed of a few to a hundred atoms, their sizes are comparable to the Fermi wavelength of electrons, resulting in molecule-like properties including discrete electronic states and size-dependent fluorescence. Fluorescent metal nanoclusters have an attractive set of features, such as ultrasmall size, good biocompatibility and excellent photostability, making them ideal fluorescent labels for biological applications. In this review, we summarize synthesis strategies of water-soluble fluorescent metal nanoclusters and their optical properties, highlight recent advances in their application for ultrasensitive biological detection and fluorescent biological imaging, and finally discuss current challenges for their potential biomedical applications. [Copyright &y& Elsevier]

Abstract: Quantum dots (QDs) are novel photostable semiconductor nanocrystals possessing wide excitation spectra and narrow, symmetrical emission spectra and can be conjugated to a wide range of biological targets, including proteins, antibodies and nucleic acid probes. These characteristics have provoked considerable interest in their use for bioimaging. Much investigation has been performed into their use for multiplex immunohistochemistry and in situ hybridisation which, when combined with multispectral imaging, has enabled quantitation and colocalisation of gene expression in clinical tissue. Many advances have recently been made using QDs for live cell and in vivo imaging, in which QD-labelled molecules can be tracked and visualised in 3-D. This review aims to outline the beneficial properties presented by QDs along with important advances in their biological application. [Copyright &y& Elsevier]

Abstract: An efficient bacterial synthesis method to harvest cadmium telluride (CdTe) quantum dots (QDs) with tunable fluorescence emission using Escherichia coli is demonstrated. Ultraviolet–visible, photoluminescence, X-ray diffraction and transmission electron microscopy analysis confirmed the superior size-tunable optical properties, with fluorescence emission from 488 to 551nm, and the good crystallinity of the as synthesized QDs. A surface protein capping layer was confirmed by hydrodynamic size, ζ potential and Fourier transform infrared spectroscopy measurements, which could maintain the viability (92.9%) of cells in an environment with a QD concentration as high as 2μM. After functionalization with folic acid the QDs were used to image cultured cervical cancer cells in vitro. Investigations of bacterial growth and morphology and the biosynthesis of CdTe QDs in Luria–Bertani medium containing E. coli-secreted proteins showed that extracellular synthesis directly relied on the E. coli-secreted proteins, and a mechanism for protein-assisted biosynthesis of QDs is proposed. This work provides an economical approach to fabricate highly fluorescent biocompatible CdTe QDs via an environmentally friendly production process. The biosynthesized QDs may have great potential in broad bio-imaging and bio-labeling applications. [Copyright &y& Elsevier]

Abstract: A large number of critical molecular and cellular events occur at the cell surface and cortex; such as cell adhesion, secretion, cytoskeletal interactions, membrane dynamics and cell wall deposition. Investigating such phenomena using many epifluorescence microscopy methods has been challenging due to less than desirable temporal resolution, signal to noise ratio, and phototoxicity. Total internal reflection fluorescence microscopy overcomes many of these difficulties and represents a viable approach for selective visualization of surface regions of fungal and other eukaryotic cell systems. [Copyright &y& Elsevier]

Abstract: In recent years, application of remote sensing to marine mammal surveys has been a promising area of investigation for wildlife managers and researchers. In April 2006, the United States and Russia conducted an aerial survey of Pacific walrus (Odobenus rosmarus divergens) using thermal infrared sensors to detect groups of animals resting on pack ice in the Bering Sea. The goal of this survey was to estimate the size of the Pacific walrus population. An initial analysis of the U.S. data using previously-established methods resulted in lower detectability of walrus groups in the imagery and higher variability in calibration models than was expected based on pilot studies. This paper describes an improved procedure for detection and enumeration of walrus groups in airborne thermal imagery. Thermal images were first subdivided into smaller 200×200 pixel “tiles.” We calculated three statistics to represent characteristics of walrus signatures from the temperature histogram for each tile. Tiles that exhibited one or more of these characteristics were examined further to determine if walrus signatures were present. We used cluster analysis on tiles that contained walrus signatures to determine which pixels belonged to each group. We then calculated a thermal index value for each walrus group in the imagery and used generalized linear models to estimate detection functions (the probability of a group having a positive index value) and calibration functions (the size of a group as a function of its index value) based on counts from matched digital aerial photographs. The new method described here improved our ability to detect walrus groups at both 2m and 4m spatial resolution. In addition, the resulting calibration models have lower variance than the original method. We anticipate that the use of this new procedure will greatly improve the quality of the population estimate derived from these data. This procedure may also have broader applicability to thermal infrared surveys of other wildlife species. [Copyright &y& Elsevier]

Abstract: Fluorescence imaging techniques are extremely powerful tools in cell biology, providing valuable insights into the structure and function of biomolecules in their native environments. In particular, the use of Förster resonance energy transfer (FRET) has become increasingly important to obtain information on interactions on the nanoscale, in turn providing insights into molecular behaviour inside living cells. This review describes the basic principles of FRET and fluorescence lifetime imaging microscopy (FLIM) and their application in analyses of protein interactions inside living fungal cells. [Copyright &y& Elsevier]

Summary: CD4 T helper cells play a central role in the control of infection by intracellular parasites. How efficiently pathogen-specific CD4 T cells detect infected cells in vivo is unclear. Here, we employed intravital two-photon imaging to examine the behavior of pathogen-specific CD4 T cells at the site of Leishmania major infection. While activated CD4 T cells enter the inflamed tissue irrespective of their antigen specificity, pathogen-specific T cells preferentially decelerated and accumulated in infected regions of the dermis. Antigen recognition by CD4 T cells was heterogeneous, involving both stable and dynamic contacts with infected phagocytes. However, not all infected cells induced arrest or deceleration of pathogen-specific T cells, and dense clusters of infected cells were poorly accessible to migrating T cells. Thus, disparities in the dynamics of T cell contacts with infected cells and local variation in T cell access to infected cells are important elements of the host-pathogen interplay. [Copyright &y& Elsevier]

The article presents a study which aims to observe the behavior of yeast in bread dough through the fluorescent bio-imaging technique. It mentions the use of host strains Escherichia coli DH5α for the control of recombinant DNA and Saccharomyces cerevisiae strain MT8-1 for the display of enhanced green fluorescent protein (EGFP). Results show that the use of fluorescent microscope helps determine the location of yeast cells in the bread dough.

Summary: Data compression is inevitable to reduce the huge data amounts of virtual slides, especially in virtual 3-dimensional (3D) microscopy. Lossy compression influences the image quality and leads to recognizable compression artifacts above a compression ratio of 20:1 in JPEG2000 format. To test out whether higher compression ratios are acceptable in diagnostic pathology, we prepared virtual 3D slides of gastric biopsy specimens with or without Helicobacter pylori gastritis using 5 different compression ratios as follows: 20:1, 40:1, 50:1, 75:1, and 200:1. The virtual 3D slides were diagnosed in a blinded manner by 3 pathologists according to the updated Sydney classification. The results showed no significant differences using virtual 3D slides with any compression of up to 200:1. We conclude that compression ratios higher than those commonly used can be applied in virtual microscopy, even in diagnostic applications. [Copyright &y& Elsevier]

Despite advances in imaging and interventional techniques, discogenic back pain continues to be a diagnostic and management challenge. Practitioners have sought the use of minimally invasive intradiscal thermal therapies for the relief of discogenic low back pain. Different techniques delivering heat to the disc have been developed, collectively known as thermal intradiscal procedures. The main focus of this review is dedicated to the most studied procedure, intradiscal electrothermal therapy (IDET), in the management of discogenic low back pain. Although IDET may be beneficial in a selected population of patients, evidence in support of wider use of IDET does not exist. The debate goes on regarding the efficacy of the available techniques. [Copyright &y& Elsevier]

Abstract: A methodical system for looking at every chest radiograph is suggested. Readers are encouraged to decide whether an opacity on a chest radiograph is due to pleural, alveolar or interstitial pathology and then to consider the cause. Lung and pleural masses are considered and contrasted and the features of asbestos exposure listed. Special consideration is given to the problems of interpretation of the chest radiograph in the intensive care unit, and the various appearances of lines and tubes are outlined. [Copyright &y& Elsevier]

This article discusses the use of imaging plates without shielding to monitor Americium exposure in the human lung. According to the authors, high energy alpha wave radiation exposure from plutonium sources has previously required bioassay or external counting methods. They argue that the lower detection limit of the imaging plate system developed by the U.S. Lawrence Livermore National Laboratory is the same as the germanium detector and the phoswich detectors. These imaging plates were sealed in lightproof bags and tested on the realistic torso phantom. They have also been used successfully with radioiodine isotopes in the thyroid.

We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 µm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti-major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study which develops dual-fluorescence probes for in vivo and in vitro imaging of RNA in a cell. The study described the synthesis of OMUpy1 and OMUpy2 with a cyanine dye. The results of a fluorescence analysis showed that the probes have yellow or pink fluorescence derived from the cyanine dyes with an extremely large Stokes shift. A brief description of color-coded fluorescence images produced in the presence of RNA targets is provided.

A trio of studies in this issue of Cell Stem Ce!! from Mirzadeh et al., Shen et al., and Tavazoie et al. use three-dimensional imaging techniques to reveal microanatomical details of the adult neural stem cell niche. Combined, the results also provide a framework for future functional studies. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a chronic infection in which intracellular parasites avoid destruction by the immune system. Using intravital imaging, demonstrate that some parasitized dendritic cells receive much less attention than others during their choreographed dance with T cells, suggesting that these “wallflowers” could allow for parasite survival. [Copyright &y& Elsevier]