Supramolecular Sequential Light-Harvesting Systems for Constructing White LED Device and Latent Fingerprint Imaging.

The fabrication of supramolecular light-harvesting systems (LHS) with sequential energy transfer is of significance in utilizing light energy. In this study, we report the non-covalent self-assembly of a sequential LHS by pillar[5]arene-based host-guest interaction in water and its applications in white light-emitting diode (LED) device and latent fingerprint imaging. The host-guest complex WP5 ⊃ ${ \supset }$ G self-assembles into nanoparticles in water and shows enhanced aggregation-induced emission (AIE) effect. The nanoparticles can be further used to construct sequential LHS with fluorescent dyes 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (DBT) and sulforhodamine 101 (SR101). Impressively, the system shows white-light emission when the molar ratio of WP5 ⊃ ${ \supset }$ G/DBT/SR101 is 1100/2/16. The material can be coated on a LED bulb to achieve white-light emission. In addition, the sequential LHS exhibit multicolor fluorescence including red emission, which have been successfully applied to high-resolution imaging of latent fingerprints. Therefore, we demonstrated a general strategy for the construction of sequential LHS in water based on macrocyclic host-guest interaction and explored its multi-functional applications in white-light LED device and imaging of latent fingerprints, which will promote future development and application of supramolecular LHSs.

Fluorescent Nanoassemblies in Water Exhibiting Tunable LCST Behavior and Responsive Light Harvesting Ability.

Responsive fluorescent nanomaterials have been received considerable attention in recent years. In this work, a bola-type amphiphilic molecule, CSO, was synthesized which contains a hydrophobic cyanostilbene core and hydrophilic oligo(ethylene glycol) (OEG) coils at both sides. The cyanostilbene group is aggregation-induced emission (AIE) active, while the OEG coils are thermo-responsive. As a result, the CSO molecules can self-assemble into blue-fluorescent nanoassemblies with lower critical solution temperature (LCST) behavior in aqueous media. It is noteworthy that the LCST behavior can be reversibly regulated with changes in concentration and the introduction of K+ . Intriguingly, fluorescence of CSO assembly shows a blue-shift upon heating. Finally, by employing CSO as a light capturing antenna and energy donor, an artificial light harvesting system with tunable emission and thermo-responsive characteristics was fabricated. This study not only demonstrates an integrated approach to create responsive fluorescent nanomaterials, but also shows great potential for producing luminescent materials and mimicking photosynthesis in nature.

[Application of Droplet-Based Microfluidics in Microbial Research].

Droplet-based microfluidics is a technology that generates and manipulates highly uniform droplets, ranging from picoliter to nanoliter droplets, in microchannels under precise control. In biological research, each droplet can be used to encapsulate a small group of cells or even a single cell, and then serve as an individual container for biochemical reaction, which is well suited for high-throughput and high-resolution biochemical analysis. In the field of microbial research, from cultivation and identification of microbes to the investigation of the spatiotemporal dynamics of microbial communities, from precise quantitation of microbiota to systematic study of microbial interactions, and from the isolation of rare and unculturable microbes to the development of genetically engineered strains, droplet microfluidic technology has played an important promotional role in all these aspects. Droplet microfluidics shows potential for becoming a basic tool for exploring single-cell microbes in microbiological research. In this review, we gave a brief overview of the technical basis of droplet microfluidics. Then, we presented its latest applications in microbial research and had some discussions, aiming to provide a reference for relevant research on microorganisms.

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives.

A number of upper rim-functionalized calix[4]thiourea cyclohexanediamine derivatives have been designed, synthesized and used as catalysts for enantioselective Michael addition reactions between nitroolefins and acetylacetone. The optimal catalyst 2 with a mono-thiourea group exhibited good performance in the presence of water/toluene (v/v = 1:2). Under the optimal reaction conditions, high yields of up to 99% and moderate to good enantioselectivities up to 94% ee were achieved. Detailed experiments clearly showed that the upper rim-functionalized hydrophobic calixarene scaffold played an important role in cooperation with the catalytic center to the good reactivities and enantioselectivities.

YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuates neurodegenerative changes induced by ß-amyloid (1-42) or double transgenic overexpression of APP and PS1 via inhibition of cyclooxygenase-2.

BACKGROUND: Ginkgo biloba has been reported to possess free radical-scavenging antioxidant activity and anti-inflammatory properties. In our pilot study, YY-1224, a terpene trilactone-strengthened extract of G. biloba, showed anti-inflammatory, neurotrophic, and antioxidant effects. RESULTS: We investigated the pharmacological potential of YY-1224 in ß-amyloid (Aß) (1-42)-induced memory impairment using cyclooxygenase-2 (COX-2) knockout (-/-) and APPswe/PS1dE9 transgenic (APP/PS1 Tg) mice. Repeated treatment with YY-1224 significantly attenuated Aß (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in COX-2 (-/-) mice. YY-1224 significantly attenuated Aß (1-42)-induced upregulation of platelet-activating factor (PAF) receptor gene expression, reactive oxygen species, and pro-inflammatory factors. In addition, YY-1224 significantly inhibited Aß (1-42)-induced downregulation of PAF-acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor γ (PPARγ) gene expression. These changes were more pronounced in COX-2 (+/+) mice than in COX-2 (-/-) mice. YY-1224 significantly attenuated learning impairment, Aß deposition, and pro-inflammatory microglial activation in APP/PS1 Tg mice, whereas it significantly enhanced PAF-AH and PPARγ expression. A preferential COX-2 inhibitor, meloxicam, did not affect the pharmacological activity by YY-1224, suggesting that the COX-2 gene is a critical mediator of the neuroprotective effects of YY-1224. The protective activity of YY-1224 appeared to be more efficacious than a standard G. biloba extract (Gb) against Aß insult. CONCLUSIONS: Our results suggest that the protective effects of YY-1224 against Aß toxicity may be associated with its PAF antagonistic- and PPARγ agonistic-potential as well as inhibition of the Aß-mediated pro-inflammatory switch of microglia phenotypes through suppression of COX-2 expression.

Chiral exploration of 6,12-diphenyldibenzo[b,f][1,5]diazocine with stable conformation.

A first optical resolution of 6,12-diphenyldibenzo[b,f][1,5]diazocine with stable boat conformation was achieved by chiral supercritical fluid chromatography (SFC). The absolute configurations of enantiomers were first assigned and determined by X-ray crystal structure based on CIP-rules. The high optical rotation and circular dichroism spectrum were well explained by electronic helix theory. Owing to the high stabilization of boat conformation, the chiral configuration could be maintained at very high temperature, more than 200 °C, which was proved by Density Functional Theory calculations.

[Effect of apigenin on dendritic cells maturation and function in murine splenocytes].

This study was designed to explore the effect of apigenin (Api) on dendritic cell (DCs) maturation and function in murine spleen cells. The single spleen cell was isolated, and then cultured with lipopolysaccharide (LPS) in the present and absence of apigenin. After 24 h, the toxicity of Api and the T cell proliferation were determined by CCK8 kit. In addition, we collected the cell-free supernatants to measure cytokine production using ELISA, collected the cells to determine the DC maturation using flow cytometry. Finally, we purified Api and/or LPS-treated CD11c+ DCs which were pulsed with ovalbumin (OVA)323−339 and then were adoptive transferred into C57BL/6 mice to detect the OVA323−339-specific T cell proliferation and T helper (Th1) and Th2 cell secreting IFN-γ and IL-4 production, respectively. We found that Api did not affect splenocyte viability, but inhibited the production of pro-inflammatory cytokine IL-1ß, IL-6 and TNF-α, not anti-inflammatory cytokine IL-10. In addition, Api inhibited the expression of co-stimulatory CD80, CD86 and MHCII of CD11c + DCs. Finally, compared to LPS+OVA DCs group, DCs from Api and LPS co-treated splenocytes (Api+LPS+DCs) impaired OVA323−339-specific T cell proliferation and the production of IFN-γ and IL-4 in CD4+ T cells, which had the similar responses with OVA+DCs. These data suggest that Api exhibits anti-inflammatory properties via inhibiting DC activation and function, as a new immune-modulator, which may induce immune-tolerance with a benefit to those with chronic inflammation.

Potential signal pathway of all-trans retinoic acid for MMP-2 and MMP-9 expression in injury podocyte induced by adriamycin.

All-trans-retinoic acid (ATRA) can regulate some specific genes expression in various tissue and cells via nuclear retinoic acid receptors (RARs), including three subtypes: retinoic acid receptor-alpha (RAR-α), retinoic acid receptor-beta (RAR-ß) and retinoic acid receptor-gamma (RAR-γ). Podocyte injury plays a pivotal role in the progression of glomerulosclerosis (GS). This study was performed to study the potential signal pathway of ATRA in the expression of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) in injury podocyte. Cells were divided into three groups: group of negative control (NC), group of injury podocyte induced by adriamycin (ADR) (AI) and group of ADR inducing podocyte injury model treated with ATRA (AA). The cells morphology changes were detected using microscope and scanning electron microscopy. MMP-2 and MMP-9 enzymic activity was detected using the gelatin zymography method. Protein and mRNA expressions of MMP-2, MMP-9, RAR-α, RAR-ß and RAR-γ were measured by western-blot and real-time RT-PCR. Enzymatic activity of MMP-2 and MMP-9 in group AA was significantly enhanced compared to AI group after ATRA-treated 24 h (p < 0.05). The protein and mRNA expressions of MMP-2/MMP-9 in group AA were significantly increased than those in group AI at both 12 and 24 h time points (p < 0.05). Compared to group AI, RAR-α and RAR-γ protein/mRNA expressions of group AA were significantly increased at both 12 and 24 h time points (p < 0.05). There was no difference for the expression of RAR-ß between group AI and group AA (p > 0.05). RAR-α protein level was positively correlated with MMP-2 or MMP-9 protein expression (p < 0.05), and RAR-γ protein level was also positively correlated with MMP-2 or MMP-9 protein expression (p < 0.05). In conclusion, ATRA may increase expression of MMP-2 and MMP-9 by the potential signal pathway of RAR-α and RAR-γ in injury podocyte induced by adriamycin, but not RAR-ß.

Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway.

BACKGROUND: Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity. OBJECTIVE: To explore whether IMQ could induce melanogenesis in melanoma cells. METHODS: The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not. RESULTS: We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity. CONCLUSIONS: Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception.

Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEAMOR neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia. Furthermore, single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons, each innervating distinct target brain regions. We found that the suppression of axon branches projecting to the parabrachial nucleus (PB) of one subtype of CEAMOR neurons alleviated persistent hyperalgesia, indicating a subtype- and axonal-branch-specific mechanism of action. Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception. Thus, this study identified the central neural circuit that underlies endogenous opioid antinociception, providing new insight into the endogenous pain modulatory mechanisms.

All-trans retinoic acid attenuates the renal interstitial fibrosis lesion in rats but not by transforming growth factor-ß1/Smad3 signaling pathway.

All-trans retinoic acid (ATRA) is an important therapeutic agent for prevention of the renal diseases. Transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling pathway is a key signaling pathway which takes part in the progression of renal interstitial fibrosis (RIF). This investigation was performed to study the effect of ATRA in RIF rats and its effect on the TGF-ß1/Smad3 signaling pathway. Sixty Wistar male rats were divided into three groups at random: sham operation group (SHO), model group subjected to unilateral ureteral obstruction (GU), model group treated with ATRA (GA), n = 20, respectively. RIF index, protein expression of TGF-ß1, collagen-IV (Col-IV) and fibronectin (FN) in renal interstitium, and mRNA and protein expressions of Smad3 in renal tissue were detected at 14-day and 28-day after surgery. The RIF index was markedly elevated in group GU than in SHO group (p < 0.01), and the RIF index of GA group was alleviated when compared with that in GU group (p < 0.01). Compared with in group SHO, the mRNA/protein expression of Smad3 in renal tissue was significantly increased in group GU (p < 0.01). However, the mRNA and protein expressions of Smad3 in renal tissue in GA group were not markedly alleviated by ATRA treatment when compared with those in GU (each p > 0.05). Protein expressions of TGF-ß1, Col-IV, and FN in GU group were markedly increased than those in SHO group (each p < 0.01), and their expressions in GA group were markedly down-regulated by ATRA treatment than those of GU group (all p < 0.01). The protein expression of Smad3 was positively correlated with RIF index, protein expression of TGF-ß1, Col-IV or FN (each p < 0.01). In conclusion, ATRA treatment can alleviate the RIF progression in UUO rats. However, ATRA cannot affect the signaling pathway of TGF-ß1/Smad3 in the progression of RIF.

Host-Guest Complexes of Pillar[5]arene as Components for Supramolecular Light-Harvesting Systems with Tunable Fluorescence.

A guest molecule containing a short alkyl spacer between the tetraphenylethylene group and the methylpyridinium group was designed and synthesized. After complexation with a water-soluble pillar[5]arene, the resulting host-guest complex can further self-assemble into fluorescence-emitting nanoparticles in water. By loading a commercially available dye Rhodamine 6G into the nanoparticles, an efficient artificial light-harvesting system with high donor/acceptor ratios (>400/1) was successfully constructed. The obtained systems show considerable antenna effects with values of more than 10 times. The system also exhibits tunable fluorescence emission behavior and can be used as a fluorescent ink for information encryption.

Potential roles of microRNAs and long noncoding RNAs as diagnostic, prognostic and therapeutic biomarkers in coronary artery disease.

Coronary artery disease (CAD), which is mainly caused by atherosclerotic processes in coronary arteries, became a significant health issue. MicroRNAs (miRNAs), and long noncoding RNAs (lncRNAs), have been shown to be stable in plasma and could thereby be adopted as biomarkers for CAD diagnosis and treatment. MiRNAs can regulate CAD development through different pathways and mechanisms, including modulation of vascular smooth muscle cell (VSMC) activity, inflammatory responses, myocardial injury, angiogenesis, and leukocyte adhesion. Similarly, previous studies have indicated that the causal effects of lncRNAs in CAD pathogenesis and their utility in CAD diagnosis and treatment, has been found to lead to cell cycle transition, proliferation dysregulation, and migration in favour of CAD development. Differential expression of miRNAs and lncRNAs in CAD patients has been identified and served as diagnostic, prognostic and therapeutic biomarkers for the assessment of CAD patients. Thus, in the current review, we summarize the functions of miRNAs and lncRNAs, which aimed to identify novel targets for the CAD diagnosis, prognosis, and treatment.

Zhou, T.B., et Al., correction: all-trans retinoic Acid treatment is associated with prohibitin expression in renal interstitial fibrosis rats. Int. J. Mol. Sci. 2012, 13, 2769-2782.

The authors wish to change Figure 2 of the paper published in IJMS [1]. The positions of H(1) and H(2) in the previous article were reversed. These errors have been amended in an amended version of the manuscript, which is available from the International Journal of Molecular Sciences website. The authors and publisher apologize for the inconvenience. [...].

All-trans retinoic acid treatment is associated with prohibitin expression in renal interstitial fibrosis rats.

This study was performed to investigate the association of prohibitin with renal interstitial fibrosis (RIF) lesion and to explore the association of all-trans retinoic acid (ATRA) treatment with prohibitin expression in RIF rats. Rats were divided into three groups: the sham operation group (SHO), the model group subjected to unilateral ureteral obstruction (UUO), and the model group treated with ATRA (GA). Renal tissues were collected at 14 and 28 days after surgery, and the relevant indicators were detected. In comparison with the SHO group, the RIF index in the UUO group was markedly elevated (p < 0.01), and the RIF index in the GA group was alleviated compared with that in the UUO group (p < 0.01). Compared with the SHO group, the expression of prohibitin (protein or mRNA) in the UUO group was significantly reduced (each p < 0.01). Prohibitin expression in the GA group was markedly increased when compared with that in the UUO (p < 0.01). The expression of TGF-ß1 (protein and mRNA), protein expressions of Col-IV, fibronectin, α-SMA and cleaved Caspase-3, ROS generation and cell apoptosis index in the UUO group were markedly higher than those in the SHO group (all p < 0.01), and their expressions in the GA group were markedly down-regulated compared to those in the UUO group (all p < 0.01, respectively). The protein expression of prohibitin was negatively correlated with the RIF index, protein expression of TGF-ß1, Col-IV, fibronectin, α-SMA or cleaved Caspase-3, ROS generation and the cell apoptosis index (each p < 0.01). In conclusion, lower expression of prohibitin is associated with the RIF, and ATRA treatment is associated with increased prohibitin, which can prevent the progression of RIF.

Self-assembled Fluorescent Nanoparticles with Tunable LCST Behavior in Water.

The development of stimuli-responsive fluorescent materials in water based on organic molecule has drawn significant interest. Herein, we designed and synthesized an amphiphilic molecule M containing a fixed tetraphenylethylene moiety (FTPE) as hydrophobic part and tri(ethylene glycol) (TEG) chains as hydrophilic part. Notably, the FTPE moiety is aggregation-induced emission (AIE) active, while the TEG chains are thermo-responsive. M can self-assemble into fluorescent nanoparticles (NPs) in water, which showed lower critical solution temperature (LCST) behavior. Moreover, its clouding point can be reversibly tuned upon the concentration variation. Interestingly, the NPs can be acted as a fluorescence thermometer in aqueous media owing to their unique AIE and LCST behaviors. Our work herein not only provides an integration strategy to construct stimuli-responsive fluorescent materials but also shows great potential in biological applications including bioimaging and biosensors.

An ultralow-acceptor-content supramolecular light-harvesting system for white-light emission.

White-light emission in donor-acceptor systems usually requires relatively high acceptor content and/or multiple acceptors to "neutralize" the primary color of donors. Herein, a cyanostilbene-bridged ditopic ureidopyrimidinone donor (CSU) was designed and synthesized, which can self-assemble into dispersed nanoparticles in water. Fascinatingly, efficient white-light emission can be realized by co-assembling 0.1% DBT into the nanoparticles through a light-harvesting strategy. This new system is further demonstrated for use in white-light encryption materials.

Imiquimod-induced ROS production causes lysosomal membrane permeabilization and activates caspase-8-mediated apoptosis in skin cancer cells.

BACKGROUND: Lysosomal cell death is induced by lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteolytic enzymes, including cathepsins (CTSs), which results in mitochondrial dysfunction and apoptosis. Imiquimod (IMQ), a synthetic TLR7 ligand, has both antiviral and antitumor activity against various skin malignancies in clinical treatment. Previously, we demonstrated IMQ not only caused lysosomal dysfunction but also triggered lysosome biogenesis to achieve lysosomal adaptation in cancer cells. OBJECTIVE: To determine whether lysosomes are involved in IMQ-induced apoptosis. METHODS: The human skin cancer cell lines BCC, A375 and mouse melanoma cell line B16F10 were used in all experiments. Cell death was determined by the Cell Counting Kit-8 (CCK-8) assay and DNA content assay. Protein expression was determined by immunoblotting. Caspase-8 activity was assessed using a fluorescence caspase-8 kit and determined by flow cytometry and confocal microscopy. RESULTS: IMQ not only induced lysosome damage but also abrogated lysosome function in skin cancer cells. IMQ-induced caspase-8 activation contributed to the processes of lysosomal cell death. Moreover, the use of ROS scavengers significantly abolished caspase-8 activation and inhibited IMQ-induced LMP. Additionally, pharmacological inhibition of CTSD not only abrogated caspase-8 activation but also rescued IMQ-induced cell death. Finally, lysosome-alkalizing agents enhanced the cytotoxicity of IMQ in vitro and in vivo. CONCLUSIONS: IMQ-induced ROS accumulation promotes LMP, releases CTSs into the cytosol, stimulates caspase-8 activation and finally causes lysosomal cell death. Lysosomal cell death and the CTSD/caspase-8 axis may play a crucial role in IMQ-induced cell death.

Supramolecular polymer-directed light-harvesting system based on a stepwise energy transfer cascade.

The design and construction of an artificial light-harvesting system in water by mimicking the energy transfer cascade in natural photosynthesis are of significant importance. Herein, we report an efficient two-step sequential energy transfer system based on quadruple hydrogen-bonded supramolecular polymeric nanoparticles. By loading two types of hydrophobic dyes as energy acceptors, excitation energy from the supramolecular polymer could be funneled efficiently to the final acceptor through the relay acceptor. The system exhibits tunable multicolor emission from blue through yellow to red, as well as white light emission.

Imiquimod Accelerated Antitumor Response by Targeting Lysosome Adaptation in Skin Cancer Cells.

Lysosomal adaptation is a cellular physiological process in which the number and function of lysosomes are regulated at the transcriptional and post-transcriptional levels in response to extracellular and/or intracellular cues or lysosomal damage. Imiquimod (IMQ), a synthetic toll-like receptor 7 ligand with hydrophobic and weak basic properties, exhibits both antitumor and antiviral activity against various skin malignancies as a clinical treatment. Interestingly, IMQ has been suggested to be highly concentrated in the lysosomes of plasmacytoid dendritic cells, indicating that IMQ could modulate lysosome function after sequestration in the lysosome. In this study, we found that IMQ not only induced lysosomal membrane permeabilization and dysfunction but also increased lysosome biogenesis to achieve lysosomal adaptation in cancer cells. IMQ-induced ROS production but not lysosomal sequestration of IMQ was the major cause of lysosomal adaptation. Moreover, IMQ-induced lysosomal adaptation occurred through lysosomal calcium ion release and activation of the calcineurin/TFEB axis to promote lysosome biogenesis. Finally, depletion of TFEB sensitized skin cancer cells to IMQ-induced apoptosis in vitro and in vivo. In summary, a disruption of lysosomal adaptation might represent a therapeutic strategy for synergistically enhancing the cytotoxicity of IMQ in skin cancer cells.