Activating Esterase D by PFD5 exerts antiviral effect through inhibiting glutathionization of LAMP1 during Senecavirus A infection.

Seneca virus A (SVA) is a newly discovered small nucleic acid virus, which can cause swine blister disease (PVD). Currently, there is no drug or vaccine. Studies have shown that SVA relies on the endolysosomal pathway to accomplish intracellular transport and release, and can disrupt lysosomal homeostasis, but its specific mechanism has not been revealed.

Two "turn on" fluorescence probes based on nitroso recognition group for detecting hydrogen sulfide.

Hydrogen sulfide is a vital signaling molecule which holds a pivotal position in numerous biological functions. In this research, two novel "OFF-ON" fluorescence probes named YNO and TNO were designed based on the nitroso recognition group to detect HS. Both YNO and TNO performed outstanding response rate and linear relationship between the fluorescence intensity and the concentration of HS.

Novel fluorescence probe for ClO in living cells: Based on FRET mechanism.

Hypochlorous acid (HClO) as a kind of reactive oxygen species (ROS) plays a vital role in many biological processes. Organic fluorescence probes have attracted great interests for the detection of HClO, due to their relatively high selectivity and sensitivity, satisfactory spatiotemporal resolution and good biocompatibility. Constructing fluorescence probes to detect HClO with advantages of large Stokes shift, wide emission gap, near infrared emission and good water solubility is still challenging.

A near-infrared fluorescent probe based FRET for ratiometric sensing of HO and viscosity in live cells.

Hydrogen peroxide (HO) and viscosity play vital roles in the cellular environment as signaling molecule and microenvironment parameter, respectively, and are associated with many physiological and pathological processes in biological systems. We developed a near-infrared fluorescent probe, CQ, which performed colorimetric and ratiometric detection of HO and viscosity based on the FRET mechanism, and was capable of monitoring changes in viscosity and HO levels simultaneously through two different channels. Based on the specific reaction of HO with borate ester, CQ exhibited a significant ratiometric response to HO with a large Stokes shift of 221 nm, a detection limit of 0.

Grp94 Inhibitor HCP1 Suppressed the Replication of SVA in BHK-21 Cells and PK-15 Cells.

Background: Glucoregulatory protein 94 (Grp94) is necessary for the post-viral life cycle and plays a quality control role in viral proteins, but the role of Grp94 in regulating viral replication in host cells is not well known. Therefore, finding a compound that can regulate Grp94 will help us to study the mechanism of viral replication. Previously, we synthesized a coumarin pyrazoline derivative HCP1 that is an effective inhibitor of Grp94.

An efficient dual-function fluorescent probe for sulfites and sulfides and its imaging application in cells.

As gas signaling molecules in organisms, SO derivatives and HS play crucial regulating roles in a series of physiological processes. Therefore, developing an assay that can accurately monitor the concentration of SO derivatives and HS in cells is extremely important for the research and treatment of related illnesses. A bifunctional probe SN-F based on FRET mechanism for SO derivatives and HS was designed.

FRET-based fluorescent probe with favorable water solubility for simultaneous detection of SO derivatives and viscosity.

The intracellular viscosity is an important parameter of the microenvironment and SO is a vital gas signal molecule. At present, some dual-response fluorescence probes for simultaneous measurements of viscosity and SO derivatives (HSO/SO) possessed poor water solubility. In this work, we developed a water-soluble fluorescence probe CIJ (0.

Dual-response and lysosome-targeted fluorescent probe for viscosity and sulfur dioxide derivatives.

Viscosity and sulfur dioxide levels are important factors to evaluate the changes of cell micro-environment because a series of diseases usually occur when they are abnormal. At present, dual-response probes that can detect both viscosity and sulfur dioxide are rare. Therefore, we developed a novel fluorescent probe CBN for simultaneous detection of sulfur dioxide and viscosity.

Identification of a new way to induce differentiation of dermal fibroblasts into vascular endothelial cells.

Background: Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs.

Methods: In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining.

A quinoline-coumarin near-infrared ratiometric fluorescent probe for detection of sulfur dioxide derivatives.

Sulfur dioxide derivatives (HSO and SO) play an important role in food preservative, antibacterial, antioxidant and other aspects, so it is urgent for us to develop more efficient detection methods to broaden their application in biochemical research and related disease diagnosis. Fluorescent probes are of particular interest because of their simplicity and high temporal and spatial resolution. Herein, we constructed a new near-infrared (NIR) fluorescence probe, CQC, composed of coumarin fluorophore and quinoline fluorophore, for detecting SO derivatives.

A ratiometric fluorescent probe for selective detection of thiophenol derivatives.

Though a number of on-off or off-on fluorescent probes have been developed for the detection of thiophenol by using its unique recognition groups, such as 2, 4-dinitrophenyl ether, 2, 4-dinitrophenyl sulfonamide, and 2, 4-dinitrophenyl sulfonate, up to now, there are few probes that can detect thiophenol by the proportional fluorescence signal. We developed a ratiometric fluorescent probe with coumarin pyridine derivative as fluorophore and 2, 4-dinitrophenyl ether moiety as the sensing unit which could be used to detect thiophenol derivatives by the aromatic nucleophilic substitution reaction. This probe (CPBPN) displayed significant change in fluorescence ratio (256 fold) to result in a more reliable analysis by self-calibration and a relatively low detection limit of 24 nM toward 4-methylthiophenol (MTP) within 30 min to achieve more sensitivity.

Two simple but effective turn-on benzothiazole-based fluorescent probes for detecting hydrogen sulfide in real water samples and HeLa cells.

Two simple turn-on fluorescent probes, containing a benzothiazole and the 2,4-dinitrobenzenesulfonyl group, were designed for detecting HS. Two probes exhibited good selectivity and high sensitivity, which were applied to detect the HS in real water samples. Probe P2 with a positive charge had better solubility than probe P1 in water; therefore, probe P2 was successfully applied to detect both the endogenous and exogenous HS in lysosomes of living HeLa cells.

Identification of a new autophagy inhibitor targeting lipid droplets in vascular endothelial cells.

Autophagy of vascular endothelial cells (VECs) plays an important role in maintaining vascular homeostasis. Lipid droplets (LDs) are organelles that can be formed in response to various stimuli, including excessive lipid or various stresses. LDs sequester toxic lipids, thereby preventing lipotoxic cell damage and have a complex relationship with autophagy.

HS probe CPC inhibits autophagy and promotes apoptosis by inhibiting glutathionylation of Keap1 at Cys434.

HS is actual an endogenous signaling gas molecule and involved in a range of cell physiological processes. However, the mechanism of endogenous HS regulating autophagy and apoptosis has not been thoroughly investigated. Here, we try to address this issue by using a HS probe, (E)-2-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)-piperazin-1-yl)-styryl)-1, 3, 3-trimethyl-3H-indol-1-ium iodide (CPC), which could react with endogenous HS.

A synergetic FRET/ICT platform-based fluorescence probe for ratiometric imaging of bisulfite in lipid droplets.

A deep-red emission and lipid droplets-targeted fluorescence probe (named ZFPy) for effective bioimaging of bisulfite was developed from flavone moiety and benzoindole derivative based on intramolecular charge transfer (ICT) and Förster resonance energy transfer (FRET) platform. ZFPy displayed promising fluorescence parameters including bright deep red fluorescence (615 nm), large Stokes shift (205 nm), extended emission window gap (140 nm), high absolute fluorescence quantum yield (4.1%) and stable emission signal output.

Discovery of new fluorescent thiazole-pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells.

A series of fluorescent thiazole-pyrazoline derivatives was synthesized and their structures were characterized by H NMR, C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure-activity relationship (SAR) of the compounds was analyzed.

A novel mitochondria-targeted ratiometric fluorescent probe for endogenous sulfur dioxide derivatives as a cancer-detecting tool.

A new mitochondria-targeted fluorescent probe RBC, constructed using a coumarin moiety which was selected as the donor and a benzothiazole derivative as the acceptor, for SO derivatives (HSO/SO) was presented. The probe designed on a new FRET platform showed high selectivity and a low detection limit. Importantly, the probe could respond to HSO/SO within 35 s.

Discovery of a fluorescigenic pyrazoline derivative targeting ubiquitin.

Despite significant process in ubiquitin modification by using traditional genetic methods, chemical small molecules that directly target and modify ubiquitin are little reported. Here, we find that a fluorescigenic pyrazoline derivative (FPD5) could do so effectively. Molecule docking revealed that lysine 11 of ubiquitin was the key contact residue.

A mitochondria-targeted fluorescent probe for the detection of endogenous SO derivatives in living cells.

A unique fluorescent probe (ZACA) for the monitoring of SO2 derivatives was developed from coumarin and benzoindoles based on FRET and ICT. ZACA exhibited an active emission signal, large Stokes shift, wide emission window distance, and high photostability. It also possessed many advantages in the ratiometric detection of HSO3-/SO32- including low detection limit and high selectivity and sensitivity.

A near-infrared and mitochondria-targeted fluorescence probe for ratiometric monitoring of sulfur dioxide derivatives in living cells.

A promising near-infrared emissive and mitochondria-targeted fluorescence probe (SNB) for the ratiometric detection of sulfur dioxide derivatives with a novel reaction mechanism was developed on the basis of FRET and the ICT platform. Probe SNB showed favorable fluorescence properties, including an active NIR emission signal (671 nm), ultra-large Stokes shift (251 nm) and an ultra-broad emission band gap (193 nm). Furthermore, SNB was applied to detect sulfur dioxide derivatives with a low detection limit (17 nM), excellent sensitivity and exceptional selectivity.

Loss of HMBOX1 promotes LPS-induced apoptosis and inhibits LPS-induced autophagy of vascular endothelial cells in mouse.

Our previous study revealed that Homeobox containing 1 (HMBOX1), essential for the survival of vascular endothelial cells (VECs), was involved in the progression of atherosclerosis. Knockdown of HMBOX1 promoted apoptosis and inhibited autophagy through regulating intracellular free zinc level in cultured VECs. In current study, in order to investigate the roles of HMBOX1 in vivo and in endothelium, we generated a knockout (KO) mouse for HMBOX1 by using transcription activator-like effector nucleases (TALENs) technology.

Enhancing autophagy protects platelets in immune thrombocytopenia patients.

Background: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder and involves increased apoptosis of platelets. Autophagy is an essential process for platelets to maintain their life and physiological functions. However, the role of autophagy in ITP platelets was previously unclear.

A new FRET-based ratiometric fluorescence probe for hypochlorous acid and its imaging in living cells.

A novel ratiometric fluorescence probe for hypochlorous acid was constructed by coumarin and pyridinium fluorophore based on the Forster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) platform. In this ICT/FRET system, the energy transfer efficiency is high to 94.3%.

Discovery of a new autophagy inducer for A549 lung cancer cells.

Biological activities of a series of fluorescent compounds against human lung cancer cell line A549 were investigated. The results showed that (E)-1,3,3-trimethyl-2-(4-(piperidin-1-yl)styryl)-3H-indol-1-ium iodide (8) and (E)-2-(5,5-dimethyl-3-(4-(piperazin-1-yl)styryl)cyclohex-2-en-1-ylidene) malononitrile (11) could inhibit the growth of A549 cancer cells in a dose and time-dependent manner. Furthermore, compound 8 could trigger autophagy and apoptosis, but not obviously induce necrosis under the stimulatory condition.