PET probes beyond ^(18)F-FDG

During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognized.At present,^18F-fluorodeoxyglucose（^18F-FDG） is the most broadly used PET probe.However,^18F-FDG also suffers many limitations.Thus,scientists and clinicians are greatly interested in exploring and developing new PET imaging probes with high affinity and specificity.In this review,we briefly summarize the representative PET probes beyond ^18F-FDG that are available for patients imaging in three major clinical areas（oncology,neurology and cardiology）,and we also discuss the feasibility and trends in developing new PET probes for personalized medicine.

A molecular probe carrying anti-tropomyosin 4 for early diagnosis of cerebral ischemia/reperfusion injury

In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.

Prediction of early-stage hepatocellular carcinoma using Onco Scan chromosomal copy number aberration data

AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.

Development of real-time PCR method for rapid detection and quantification of Heterosigma akashiwo

To rapidly detect the harmful algae H.akashiwo qualitatively and quantitatively, sequences of the 18S rDNA deduced from H.akashiwo were used for designing species-specific primers, and a RFQ-PCR (Real-time Fluorescent Quantitative Polymerase Chain Reaction) method was developed for quantitative detection of H.akashiwo. Primer H.akashiwo and TaqMan probe were designed, and the specificity of primer was checked with PCR. A calibration curve was constructed with cycle threshold value against visual counted cell number. And the value of the curve was tested with other H.akashiwo samples, which were assayed with both the RFQ-PCR method and visual count under microscope.

Monitoring Cr(Ⅵ)photoreduction at different depths by operando low-field NMR relaxometry

Chromium(VI)(Cr(VI)),a toxic metal ion,is widely present in industrial wastewater.To reduce the contamination of Cr(VI),many technologies for the photocatalytic reduction of Cr(VI)to Cr(III)have been developed in the past decades.However,the practical application of photocatalysts for the reduction of Cr(VI)inwastewater treatment is often hindered by the complicated photoreduction processes due to the sedimentation and stratification of catalyst particles that present during the treatment of the wastewater.Probing and understanding the influences of the sedimentation and stratification of the catalyst particles on the photoreduction processes are long-term challenges in the field.Herein,we demonstrate that this issue can be solved by using layer location integrated low-field time-domain nuclear magnetic resonance(LF-NMR)relaxometry.With paramagnetic Cr(III)cation as the molecular probe,we successfully monitored the Cr(VI)photoreduction processes by operando probing the 1 H T2 relaxation time of the photoreduction systems.The influences of catalyst sedimentation and the light wavelength on photocatalysis were studied and discussed.The results showed the great potential of LF-NMR relaxometry in the study of Cr(VI)photoreduction processes during industrial wastewater treatments.

Tuberculous Otitis Media—A Rare Entity or a Missed Diagnosis

Objective: The aim of the study is to look for indicators of Tuberculous Otitis Media in all cases of chronic suppurative otitis media. Study Design: This is a retrospective study. Setting: This study was conducted in a tertiary care centre. Subjects and Methods: Detected cases of tuberculous otitis media (TBOM) cases studied retrospectively from January 2011 to December 2013 were included in the study. Investigations for tuberculosis were considered in the cases showing suspicious pale granulation tissue in the external auditory canal and middle ear and also in cases showing exuberant pale granulation tissue during mastoid surgery where Zeihl Nielson staining, histopathology, molecular genetic study was done. Cases showing positive result were included in the study. Results: During the study period 751 cases of CSOM were seen in outpatient room of which 18 cases of TBOM were diagnosed. Three patients were diagnosed preoperatively and 181 underwent surgery of which 15 cases were diagnosed positive, from the tissue obtained during the procedure. Direct smear was positive in four cases, concentration techniques in seven cases. Line probe assay was taken as diagnostic in all the cases. None of the cases were positive on histopathology. Conclusion: Tuberculous otitis media is often missed as the classical features are not seen in all cases of TBOM. The absence of these should not stop the clinician from diagnosing the disease. Suspicious tissue should therefore be tested properly to avoid missing the diagnosis and to prevent any complications.

Investigation of Edge Fluctuation Characteristics on the HL-2A Tokamak

The edge plasma fluctuation characteristics are studied by the fast reciprocating scanning 6-probes in the boundary region. These probes can measure edge plasma temperature, density, poloidal electric field, radial electric field, Reynolds stress, and their profiles in once discharges. Measurement results are used to analyze plasma confinement, turbulent fluctuations and their correlation characteristics during multi-shot pellet injection （MPI） , supersonic molecular beam injection （SMB1） and electron cyclotron resonant heating （ ECRH ） discharges.

5-Ethynyl-2′-deoxyuridine as a molecular probe of cell proliferation for high-content siRNA screening assay by “click” chemistry

Labelling and identification of proliferating cells is important for the study of physiological or pathological processes in high-content screening (HCS) assays. Here we describe ethynyl deoxyuridine (EdU) as a biomarker for the assessment of cell proliferation and clearly demonstrate the feasibility of the EdU-labelling method for use in HCS assays. EdU detection is highly robust, reproducible, technically simple, and well suited for automated segmentation, which provides an excellent al- ternative for setting up multiplexed HCS assays of siRNA, miRNA and small-molecule libraries.

Molecular imaging of enzyme activity in vivo using activatable probes

Precise measurement of enzyme activity in living systems with molecular imaging probes is becoming an important technique to unravel the functional roles of different enzymes in biological processes. Recent progress has been made in the development of a myriad of molecular imaging probes featuring different imaging modalities, including optical imaging, magnetic resonance imaging, nuclear imaging, and photoacoustic imaging, allowing for non-invasive detection of various enzyme activities in vivo with high sensitivity and high spatial resolution. Among these imaging probes, activatable or ＂smart＂ probes, whose imaging signal can be specifically switched from the ＂off＂ to ＂on＂ state upon interaction with a target enzyme, are particularly attractive due to their improved sensitivity and specificity. Here, recent advances in the development of activatable probes capable of imaging different enzyme activities in vivo are summarized based on different imaging modalities, and current challenges and future perspectives are discussed.

Novel strategy for accurate tumor labeling:endogenous metabolic imaging through metabolic probes

Altered metabolism has long been recognized as a central hallmark of cancer;however,in the fluorescence imaging field,few studies have been conducted to label tumors by exploiting metabolic differences between cancer cells and normal cells.In this work,we successfully developed a metabolic probe MB-C for specific imaging of glutathione(GSH)dynamic metabolic pathways.GSH was endogenously metabolized to produce SO_(2)via Na_(2)S_(2)O_(3) and thiosulfate sulfurtransferase,equilibrating with sulfites/bisulfites.MB-C was allowed to be activated by GSH along with multi-fluorescence emission increased in red and green channels and further sequence-response metabolites(SO_(2))of GSH in significant fluorescence ratio change of red and green channels.Furthermore,such evident fluorescence ratio changes could be used to distinguish cancer cells from normal cells and identify tumor and normal tissues.Therefore,GSH metabolic imaging was successfully applied to accurately label tumors,which provides a new idea and practical case for the precise visualization of malignant tumors.

Visualizing Macrophage Phenotypes and Polarization in Diseases:From Biomarkers to Molecular Probes

Macrophage is a kind of immune cell and performs multiple functions including pathogen phagocytosis,antigen presentation and tissue remodeling.To fulfll their functionally distinct roles,macrophages undergo polarization towards a spectrum of phenotypes,particularly the classically activated(M1)and alternatively activated(M2)subtypes.However,the binary M1/M2 phenotype fails to capture the complexity of macrophages subpopulations in vivo.Hence,it is crucial to employ spatiotemporal imaging techniques to visualize macrophage phenotypes and polarization,enabling the monitoring of disease progression and assessment of therapeutic responses to drug candidates.This review begins by discussing the origin,function and diversity of macrophage under physiological and pathological conditions.Subsequently,we summarize the identifed macrophage phenotypes and their specifc biomarkers.In addition,we present the imaging probes locating the lesions by visualizing macrophages with specifc phenotype in vivo.Finally,we discuss the challenges and prospects associated with monitoring immune microenvironment and disease progression through imaging of macrophage phenotypes.

Principle and Experiment of Protein Detection Based on Optical Fiber Sensing

A method for detecting protein molecules based on the tilted fiber Bragg grating （TFBG） surface plasma resonance （SPR） is proposed to achieve the quick online real-time detection of trace amount of proteins. The detection principles of the TFBG-SPR protein molecular probe are analyzed, and its feasibility is demonstrated. The intermediary material between the protein molecules and the golden layer outside of the fiber gratings is cysteamine hydrochloride. When the concentration of the cysteamine hydrochloride solution is 2 M, the shift of the TFBG resonance peak is 2.23 nm, illustrating that the cysteamine hydrochloride modifies the gold film successfully. IgG antigen solution is poured on the surface of the cysteamine hydrochloride modifying the gold-deposited TFBG. Finally, antigen-antibody hybridization experiment is carried out with a 10mg/mL antibody solution, and after two hours of hybridization the resonance peak of the TFBG shifts 5.1 nm, which validates the feasibility and effectiveness of the TFBG-SPR protein molecular probe.

Design and synthesis of biotinylated dimethylation of alkannin oxime derivatives

DMAKO-05,a novel dimethylation of alkannin oxime derivative,exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colorectal carcinoma and melanoma.However,its potent cytotoxicity is not closely associated with reactive oxygen species（ROS） and bioreductive alkylation.Its specific antitumor target（s） has still remained elusive.To recognize the molecular target（s） of DMAKO-05 and its analogs,four biotinylated DMAKO derivatives were designed and prepared.The biotin moiety was successfully introduced in the molecule through a modified Mitsunobu reaction,which kept its anticancer activity.Moreover,the cellbased investigation demonstrated that replacement of the linker C4 chain with another alkyl chain（C6 or C8） gave rise to the enhancement of cytotoxicity.Among these biotinyl derivatives,both compound 16 and 8c exhibited more potent anticancer activity than DMAKO-05 against MCF-7 cells and were comparatively effective to alkannin toward HCT-15 cells.As expected,they might be thought as ideal chemical probes.Collectively,our present work could provide an available approach for the identification of the potential antineoplastic target（s） of DMAKO derivatives.

Chemiluminescence:From mechanism to applications in biological imaging and therapy

Chemiluminescence(CL)is an emission phenomenon induced by chemical reaction.Different from the photoluminescence,CL is free from external excitation source,which is expected to show great advantages such as higher signal-to-background ratio(SBR)in bioimaging,and deeper tissue penetration in photodynamic therapy(PDT).This review introduces the theoretical aspects of CL mechanism,such as classification,energy consideration and chemiexcited/photoexcited states.Application of CL in bioimaging is highlighted.In particular,the approaches to modulate the brightness and the wavelength of CL are summarized,which are two fundamental parameters in bioimaging.Finally,the application of CL in PDT is introduced.The potential challenges and perspectives of CL in bioimaging and therapy are also discussed.

Progress in the application of molecular imaging inpsychiatric disorders

Psychiatric disorders have always attracted a lot of attention from researchers due to the difficulties in their diagnoses and treatments.Molecular imaging,as an emerging technology,has played an important role in the researchers of various diseases.In recent years,molecular imaging techniques including magnetic resonance spectroscopy,nuclear medicine imaging,and fluorescence imaging have been widely used in the study of psychiatric disorders.This review will briefly summarize the progression of molecular imaging in psychiatric disorders.