Small-molecule chemical probes for the potential therapeutic targets in alcoholic liver diseases

Alcoholic liver disease(ALD)encompasses a range of conditions resulting from prolonged and excessive alcohol consumption,causing liver damage such as alcoholic fatty liver,inflammation,fibrosis,and cirrhosis.Alcohol consumption contributes to millions of deaths each year.So far,the effective treatments for ALD are limited.To date,the most effective treatment for ALD is still prevention by avoiding excessive alcohol consumption,and only few specialized medicines are in the market for the treatment of patients suffering from ALD.Small molecules targeting various pathways implicated in ALD pathogenesis can potentially be used for effective therapeutics development.In this review,we provide a concise overview of the latest research findings on potential therapeutic targets,specifically emphasizing small-molecule interventions for the treatment and prevention of ALD.

Recent advances in the targeted fluorescent probes for the detection of metastatic bone cancer

Tumors of the breast,prostate,and lung are most likely to metastasize to the bone and typically indicates a poor cure and survival rate in cancer patients.Detection of metastatic bone cancer in early stage would save many lives and greatly improve patients’quality of life.Clinically,bone scintigraphy is often utilized to visualize bone metastases due to its relatively low cost and high sensitivity.Recently,a growth number of analytical researches aimed at developing targeted fluorescent probes to noninvasively image bone metastases with improved spatial resolution and specificity has been reported.In this review,we will summarize and discuss the recent published fluorescent probes on the accurate detection of metastatic bone cancer.First,the design principles of various targeted probes for imaging bone metastases will be presented,highlighting the signal moieties,targeting ligands,and physicochemical properties of the bone-specific probes.Next,the up-to-date bone-targeting fluorescent probes will be summarized and overviewed.Finally,future perspectives and challenges confronting the researchers in this field will be discussed.We believe this review will encourage novel ideas to develop smart targeted molecular probes for bone metastasis imaging,image-guided surgery,and therapeutic imaging materials.

Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade.Only a few nontargeted dyes,including indocyanine green and methylene blue,are currently applied for fluorescence guided surgery in the clinic.While no targeted fluorescent probes have been approved for the clinic,a number of them have entered clinical trials.These probes have emission wavelengths in the visible and near infrared(NIR)-I(700-900 nm)range.Among them,activatable probes and nanoprobes have generated special interest.Compared with NIR-I fluorescent probes,NIR-II(1000-1700 nm)fluorescent probes exhibit better intravital performance in terms of increased penetration depths,reduced tissue autofluorescence,and higher signalto-background ratios.However,more challenges are expected before the successful translation of NIR-II probes from bench to bedside.This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR-II fluorescence imaging.In addition,we outline key considerations concerning the design of fluorescent probes for clinical translation.

Light controlled imaging probes for intracellular target recognition： photochromism as a tool to enhance sensing precision

Chemosensors and imaging probes have been the focus of significant research interest over the past few decades.In part due to ease of preparation and simplicity in manipulation,fluorescent probes have been extensively used for biomedical applications.When used for in vitro cell imaging[1,2]。

Experimental study on pulse radar target probing in RFS based on interrupted transmitting and receiving

Radar target probing and measurement are challenging tasks for Radio Frequency Simulation（RFS） with pulse radar signal. Due to the long-time duration of pulse radar signal and the limited space of anechoic chamber, the reflected signal returns before pulse radar signal is fully transmitted in RFS. As a consequence, the transmitted and reflected signals are coupled at the receiver. To handle this problem, the Interrupted Transmitting and Receiving（ITR） experiment system is constructed in this paper by dividing the pulse radar signal into sub-pulses. The target echo can be obtained by transmitting and receiving the sub-pulses intermittently. Furthermore, the principles of ITR are discussed and the target probing experiments are performed with the ITR system. It is demonstrated that the ITR system can overcome the coupling between the reflected and transmitted signals. Based on the target probing results, the performance of pulse radar target probing and measurement can be verified in RFS with the ITR system.

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.