Fluorescent probes for biothiols have aroused increasing interest owing to their potential to enable better understanding of the diverse physiological and pathological processes related to the ...biothiol species. BODIPY fluorophores exhibit excellent optical properties, which can be readily tailored by introducing diverse functional units at various positions of the BODIPY core. In the present review, the development of fluorescent probes based on BODIPYs for the detection of biothiols are systematically summarized, with emphasis on the preferable detection of individual biothiols, as well as simultaneous discrimination among cysteine (Cys), homocysteine (Hcy), reduced glutathione (GSH). In addition, organelle‐targeting probes for biothiols are also highlighted. The general design principles, various recognition mechanisms, and biological applications are elaboratively discussed, which could provide a useful reference to researchers worldwide interested in this area.
Biothiol probes: The development of BODIPY‐based fluorescent probes for the detection of biothiols, preferable detection of individual biothiols, as well as simultaneous discrimination among Cys, Hcy, and reduced glutathione (GSH) is systematically summarized.
Within educational philosophy and theory, there has been an international re-turn to envision
study
as an alternative formation to disrupt the defining
learning
logic. As an enrichment, this paper ...articulates “Daoist onto-un-learning” as an Eastern form of
study
, drawing upon Roger Ames’s (Confucian role ethics: a vocabulary, Chinese University Press, Hong Kong,
2011
) interpretation of the ancient Chinese correlative cosmology and relational personhood thinking. This articulation is to dialogue with the conceptualizations of
study
(
with
) shared by Giorgio Agamben, Derek Ford, and Tyson Lewis, and unfolds in three steps. First, I examine how their conceptualizations of
study
(
with
) constrain the
studier
-
doing
-
study
logic as a commonsensical expression of “foundational individualism” (Rosemont and Ames in Confucian role ethics: a moral vision for the 21st century?, VetR Unipress, Göttingen,
2016
) and anthropocentric disordering (Harari in Sapiens: a brief history of humankind, Vintage, London,
2015
). Second, re-invoking the ancient Chinese wisdom, I envision “Daoist onto-un-learning” as a non-individualistic and non-anthropocentric form of
study
, re-configuring study and learning no longer as two disparate, if not necessarily oppositional, formations but into a Daoist bipolar yin-yang movement. Finally, I story-tell my doctoral research experience as a Daoist onto-un-learning journey, a spiralling learning-study movement, to unpack the ways it suspends and overturns the modern-Western(nized) trap/trope of anthropocentric-foundational individualism. In so doing, this paper further internationalizes and supplements the current
study
scholarship in relation to learning in a way so-far hardly explored yet cross-culturally provocative.
Friction properties of carbon nanodiamond (CND) and nanoscroll (CNS formed from graphene patch wrapping around nanodiamond) were studied by nonequilibrium molecular dynamic simulation of sliding ...diamond-like carbon (DLC) over the nanoparticles supported by amorphous silica (a-SiO2) slabs. CNS reduces friction coefficient (COF) by 72% relative to CND and superlubricity (COF ≤ 0.01) is enabled by CNS, which agrees well with experimental observations. Due to the wrapping graphene patch, the DLC-CNS contact area is smaller than the DLC-CND contact area and the CNS motion is repressed. Contrary to the rolling motion of ball bearings at the macroscale, the repressed motion of nanoparticles reduces the system friction dissipation. These make CNS a more effective solid lubricant compared with CND.
Display omitted
•Effect of contact area and nanoparticle motion on the friction properties of CND and CNS was studied.•The CNS reduces friction coefficient (COF) by 72% relative to the CND.•The lower contact area leads to lower friction force for the CNS system compared with the CND system.•The nanoparticle motion provides an additional energy dissipation channel and increase system friction dissipation.•The repressed CNS motion causes less friction dissipation compared with the CND.
Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the ...underlying molecular mechanisms have not been clearly elucidated.
The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay. Cell cycle distribution and apoptosis were examined by flow cytometry. Transmission electron microscopy was used to visualized autophagosomes. Activation of AMPK and inhibition of mTORC1/C2 pathways was assessed by Western blot analysis. RPMI8226 cells and U266 cell lines with AMPK knockdown were generated by transfection with small interfering RNA targeting the AMPK-α1 and α2 subunits using Lipofectamine 2000 reagent.
Metformin effectively inhibited the proliferation of MM cell lines, an effect that was associated with the induction of autophagy and G0/G1 cell cycle arrest, but not apoptosis. Metformin activated AMPK and repressed both mTORC1 and mTORC2 signaling pathways in myeloma cells as well as downstream molecular signaling pathways, such as p-4EBP1 and p-AKT. AMPK activation resulted in direct phosphorylation and activation of tuberous sclerosis complex 2 (TSC2), leading to inhibition of the mammalian target of rapamycin (mTOR). In addition, metformin inhibited myeloma cell growth in an AMPK-dependent manner. The xenograft mouse model further confirmed that metformin inhibited tumor growth by upregulation of AMPK and downregulation of mTOR.
Metformin inhibits the proliferation of myeloma cells by inducing autophagy and cell-cycle arrest. Our results suggest that the molecular mechanism involves dual repression of mTORC1 and mTORC2 pathways via AMPK activation. Our study provides a theoretical basis for the development of novel strategies for the treatment of MM using metformin as an already approved and safe drug.
Biothiols, such as glutathione (GSH), homocysteine (Hcy) and cysteine (Cys), are important biomarkers and play crucial roles in many physiological processes. Thus, the detection of biothiols is ...highly important for early diagnosis of diseases and evaluation of disease progression. Herein, new types of BODIPY-based fluorescent probes (probe 1, probe 2 and probe 3) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids were developed. In addition, we further studied the influence of different electronegativity substituents on these probes to sensing Cys/Hcy. Ultimately, we concluded that the electron withdrawing group on probe 1 can accelerate the probe response to Cys/Hcy, and probe 1 was successfully applied for selective imaging Cys/Hcy in living cells.
Display omitted
•A series of novel BODIPY-based fluorescent probes for cysteine and homocysteine were developed.•All three fluorescent probes have advantage of high sensitivity and selectivity.•Probe 1 was capable of detecting Cys/Hcy in living cells.
A novel turn-on red fluorescent BODIPY-based probe (Probe 1) for the detection of glutathione was developed. Such a probe carries a para-dinitrophenoxy benzyl pyridinium moiety at the meso position ...of a BODIPY dye as self-immolative linker. Probe 1 responds selectively to glutathione with the detection limit of 109nM over other amino acids, common metal ions, reactive oxygen species, reactive nitrogen species, and reactive sulfur species. A novel electrostatic interaction to modulate the SNAr attack of glutathione was believed to play significant role for the observed selective response to glutathione. The cleavage of dinitrophenyl ether by glutathione leads to the production of para-hydroxybenzyl moiety which is able to self-immolate through an intramolecular 1,4-elimination reaction to release the fluorescent BODIPY dye. The low toxic probe has been successfully used to detect mitochondrial glutathione in living cells.
A novel turn-on red fluorescent BODIPY-based probe (Probe 1) for the detection of GSH wes developed. Such a probe carrys a para-dinitrophenoxy benzyl pyridinium moiety at meso position as self-immolative linker. A novel electrostatic interaction to modulate the SNAr attack of GSH was believed to play significant role for the observed selective response to GSH. Such a probe is low toxic and has been successfully used to detect mitochondrial GSH in living cells.
Display omitted
•A novel turn-on red fluorescent BODIPY-based probe for the detection of GSH was developed.•The probe carries a para-dinitrophenoxy benzyl pyridinium moiety at the meso position of a BODIPY dye as self-immolative linker.•The probe displayed sensitivity and selectivity for GSH.•The probe have been used to detect mitochondrial GSH in living cells.
Cysteine (Cys) is a crucial bio-thiol attributing to its significant role in many physiological and pathological processes and maintaining redox dynamic balance. In mitochondria, ROS can cause ...oxidative damage, and Cys can solve this problem by acting as an antioxidant. Herein, we designed and synthesized a series of meso-pyridin and meso-pyridinium substituted BODIPY dyes as fluorescent probes to distinguish Cys. Through screening the responsive behaviors of the all probes toward biothiols, we obtained an appropriate mitochondria-targeted probe BDP-S-o-Py+ for Cys-specific detection. Density functional theory (DFT) calculations were used to demonstrate the different reactivity of the probes. BDP-S-o-Py+ could detect Cys with fast response under biological environment. The probe BDP-S-o-Py+ had a low limit of detection (LOD, 72 nM) at the linear dynamic range from 0 to 50 μM. In particularly, BDP-S-o-Py+ could be used for imaging of mitochondrial Cys in living cells, and was capable of monitoring endogenous Cys in vivo, successfully.
Display omitted
•An appropriate mitochondria-targeted probe BDP-S-o-Py+ for detection of Cys was obtained by screening synthesized dyes•The different reactivity of probes was demonstrated by density functional theory (DFT) calculations.•BDP-S-o-Py+ could detect Cys with fast response, high sensitivity and selectivity.•BDP-S-o-Py+ was successfully used to image mitochondrial Cys in HeLa cells.•BDP-S-o-Py+ was capable of monitoring endogenous Cys in vivo.
The development of metallacycles with high stability and intense near-infrared (NIR) absorption is important for biomedical applications. However, very few molecular design strategies have been ...developed on such metallacycles. Herein, we report a new series of stable and well-defined NIR-absorbing metallacycles (M1–M3) through the Pt–acetylide coordination with highly efficient photoconversion performance for cancer phototherapy. The metallacycles showed high stability and strong NIR absorption, and the absorption peaks were red shifted approximately 30 nm in comparison with their corresponding precursors. The introduction of Pt into metallacycles promotes significant photoconversions, including the singlet-to-triplet and nonradiative transitions. Moreover, the fabricated M3 nanoparticles (M3-NPs) showed favorable photoconversions into both thermal effect and singlet oxygen generation upon NIR irradiation, achieving tumor ablation. This novel design of Pt-acetylide metallacycles possesses not only complex topological architectures but also a valuable paradigm for precise cancer phototherapy, which is important for grafting stimuli-responsive functional groups into metallacycles for the development of high-performance biomedical supramolecular materials.
A new selective fluorescent and colorimetric chemosensor for the detection of GSH was developed. The discrimination of GSH from Cys and Hcy is achieved through two emission channel detection. The ...detection limit of probe 1 for GSH reached 10 nM (3 ppb). The excellent sensitivity and selectivity of probe 1 allow the selective detection of GSH over Cys and Hcy, which can be visualized colorimetrically and/or fluorescently. The sensitive detection of GSH allowed for convenient measurement of the GSH content in human plasma. The presence of GSH in cells was demonstrated through cell imaging.
The hotel management relationship is a good business strategy for hotels, which can promote the development of a hotel, when a classification algorithm is applied to customer relationship management ...system. First, the classification algorithm is based on a support vector machine is studied, the nearest neighbor sample density is used, and the corresponding mathematical model is constructed. Second, the procedure of a classification algorithm based on fuzzy support vector machine is designed. Third, a customer acquisition plan based on a classification algorithm is analyzed. Finally, a hotel is used as the research object, and a customer acquisition analysis is carried out, and the results show that the new method has quicker training speed and higher classification correctness.
PDF
