Fabrication of optical fiber tapers is realized with a combination of plasmonic microheaters and specially designed structural bending of optical fibers, which provide the necessary elements of "heat ...and pull". The resultant compactness and flame-free condition enable monitoring of the tapering process inside a scanning electron microscope.
Traditional therapeutic and diagnostic tools exhibit serious side effects, poor selectivity, and sensitivity. Herein, a multifunctional CuPc@HG@BN theranostic platform composed of hexagonal boron ...nitride nanosheets (h‐BNNS), conjugated DNA oligonucleotide, and copper(II) phthalocyanine (CuPc) was developed in which the CuPc molecule played double key roles in photodynamic therapy (PDT) as well as in situ monitoring and imaging of miR‐21 by surface‐enhanced Raman spectroscopy (SERS). Owing to the designed circle amplification of miRNA and high SERS effects of CuPc on h‐BNNS, miR‐21 responsive concentration was achieved as low as 0.7 fm in live cells. Both in vitro and in vivo data demonstrated that the integrated nanoplatform showed remarkable enhancement in PDT efficiency with minimized damage to the normal tissues. The developed probe was also successfully utilized for early monitoring and guiding the early therapy, realizing tumor elimination.
A theranostic nanoplatform composed of h‐BN nanosheets, conjugated DNA oligonucleotide, and copper(II) phthalocyanine was constructed for SERS in situ monitoring of miR‐21 and photodynamic therapy. Real‐time monitoring of miR‐21 with this ultrasensitive, highly selective, and accurate theranostic nanoplatform has been successfully utilized for guiding early theranostics to improve breast cancer therapy efficiency.
Cancer is a serious threat to human life and social development and the use of scientific methods for cancer prevention and control is necessary. In this study, HQSAR, CoMFA, CoMSIA and TopomerCoMFA ...methods are used to establish models of 65 imidazo4,5-
pyridine derivatives to explore the quantitative structure-activity relationship between their anticancer activities and molecular conformations. The results show that the cross-validation coefficients
of HQSAR, CoMFA, CoMSIA and TopomerCoMFA are 0.892, 0.866, 0.877 and 0.905, respectively. The non-cross-validation coefficients
are 0.948, 0.983, 0.995 and 0.971, respectively. The externally validated complex correlation coefficients
of external validation are 0.814, 0.829, 0.758 and 0.855, respectively. The PLS analysis verifies that the QSAR models have the highest prediction ability and stability. Based on these statistics, virtual screening based on
group is performed using the ZINC database by the Topomer search technology. Finally, 10 new compounds with higher activity are designed with the screened new fragments. In order to explore the binding modes and targets between ligands and protein receptors, these newly designed compounds are conjugated with macromolecular protein (PDB ID: 1MQ4) by molecular docking technology. Furthermore, to study the nature of the newly designed compound in dynamic states and the stability of the protein-ligand complex, molecular dynamics simulation is carried out for N3, N4, N5 and N7 docked with 1MQ4 protease structure for 50 ns. A free energy landscape is computed to search for the most stable conformation. These results prove the efficient and stability of the newly designed compounds. Finally, ADMET is used to predict the pharmacology and toxicity of the 10 designed drug molecules.
The genetically encoded fluorescent sensors convert chemical and physical signals into light. They are powerful tools for the visualisation of physiological processes in living cells and freely ...moving animals. The fluorescent protein is the reporter module of a genetically encoded biosensor. In this study, we first review the history of the fluorescent protein in full emission spectra on a structural basis. Then, we discuss the design of the genetically encoded biosensor. Finally, we briefly review several major types of genetically encoded biosensors that are currently widely used based on their design and molecular targets, which may be useful for the future design of fluorescent biosensors.
MicroRNAs (miRNAs) have emerged as critical modulators of ECs function and play a vital role in the development of cardiovascular disease. Among them, miR-126 is a crucial regulator of ...atherosclerosis. Endothelial cells (ECs) death and autophagy have been described in cells to cope with the progression of atherosclerosis. Hence, the aim of this study is to investigate the effects of miR-126 on atherosclerosis in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells (HUVECs) and the potential roles of autophagy flux in these processes. Our results showed that miR-126 level was significantly reduced in ox-LDL-treated HUVECs and miR-126 overexpression induced by miR-126 mimics remarkably blocked ox-LDL-induced HUVECs injury as evidenced by the reduced cell viability, and the increased LDH release, caspase-3 activity and apoptosis ratio. In addition, ox-LDL increased LC3-II, Beclin 1, and p62 expressions in HUVECs, while these changes were nullified in the presence of treatment with bafilomycin A1 (BafA1, an inhibit autophagic flux inhibitor). However, we found that ox-LDL-induced impaired autophagy flux was recused by miR-126 mimics. Subsequently, we found that Bafi A1 pretreatment reversed the protection of miR-126 mimics against ox-LDL-induced HUVECs injury. Finally, our results showed that miR-126 mimics rescued ox-LDL-induced impaired autophagy flux through inhibiting PI3K/Akt/mTOR signaling. Taken together, our findings suggested that miR-126 alleviates ox-LDL-induced HUVECs injury through restoring autophagy flux via repressing PI3K/Akt/mTOR pathway, and further implicate the potential therapeutic targets to reverse atherosclerosis.
•MiR-126 overexpression induced by miR-126 mimics reverses ox-LDL-induced HUVECs injury.•Ox-LDL induces the impairment of autophagy flux in HUVECs.•MiR-126 mimics mitigate ox-LDL-induced HUVECs injury through rescuing autophagy flux.•MiR-126 mimics restore ox-LDL-induced impaired autophagy flux through inhibiting PI3K/Akt/mTOR pathway in HUVECs.
A biosensor was created for the simultaneous monitoring of endogenous H2Sn and H2S in mouse brains and exploring their roles in activation of the TRPA1 channel under two types of brain disease ...models: ischemia and Alzheimer's disease (AD). Based on DFT calculations and electrochemical measurements, two probes, 3,4‐bis((2‐fluoro‐5‐nitrobenzoyl)oxy)‐benzoic acid (MPS‐1) and N‐(4‐(2,5‐dinitrophenoxy) phenyl)‐5‐(1, 2‐dithiolan‐3‐yl)pentanamide (MHS‐1), were synthesized for specific recognition of H2Sn and H2S. Through co‐assembly of the two probes at the mesoporous gold film with good anti‐biofouling ability and electrocatalytic activity, this microsensor showed high selectivity for H2Sn and H2S against potential biological interferences. The biosensor can simultaneously determine the concentration of H2Sn from 0.2 to 50 μm, as well as that of H2S from 0.2 to 40 μm. The expression of TRPA1 protein positively correlated with levels of H2Sn under both ischemia and AD.
A single electrochemical sensor was created for simultaneous detection of H2Sn and H2S in the brain. The expression of TRPA1 channel was found to be positively correlated with the levels of H2Sn in two brain disease models under ischemia and Alzheimer's diseases, and H2Sn is more active for expression of TRPA1 protein than that of H2S.
Flavonoids, a class of polyphenol secondary metabolites, are presented broadly in plants and diets. They are believed to have various bioactive effects including anti-viral, anti-inflammatory, ...cardioprotective, anti-diabetic, anti-cancer, anti-aging, etc. Their basic structures consist of C6C3C6 rings with different substitution patterns to produce a series of subclass compounds, and correlations between chemical structures and bioactivities have been studied before. Given their poor bioavailability, however, information about associations between structure and biological fate is limited and urgently needed. This review therefore attempts to bring some order into relationships between structure, activity as well as pharmacokinetics of bioactive flavonoids.
Nanoparticles are promising scaffolds for applications such as imaging, chemical sensors and biosensors, diagnostics, drug delivery, catalysis, energy, photonics, medicine, and more. Surface ...functionalization of nanoparticles introduces an additional dimension in controlling nanoparticle interfacial properties and provides an effective bridge to connect nanoparticles to biological systems. With fascinating photoluminescence properties, carbon dots (C-dots), carbon-containing nanoparticles that are attracting considerable attention as a new type of quantum dot, are becoming both an important class of imaging probes and a versatile platform for engineering multifunctional nanosensors. In order to transfer C-dots from proof-of-concept studies toward real world applications such as in vivo bioimaging and biosensing, careful design and engineering of C-dot probes is becoming increasingly important. A comprehensive knowledge of how C-dot surfaces with various properties behave is essential for engineering C-dots with useful imaging properties such as high quantum yield, stability, and low toxicity, and with desirable biosensing properties such as high selectivity, sensitivity, and accuracy. Several reviews in recent years have reported preparation methods and properties of C-dots and described their application in biosensors, catalysis, photovoltatic cells, and more. However, no one has yet systematically summarized the surface engineering of C-dots, nor the use of C-dots as fluorescent nanosensors or probes for in vivo imaging in cells, tissues, and living organisms. In this Account, we discuss the major design principles and criteria for engineering the surface functionality of C-dots for biological applications. These criteria include brightness, long-term stability, and good biocompatibility. We review recent developments in designing C-dot surfaces with various functionalities for use as nanosensors or as fluorescent probes with fascinating analytical performance, and we emphasize applications in bioimaging and biosensing in live cells, tissues, and animals. In addition, we highlight our work on the design and synthesis of a C-dot ratiometric biosensor for intracellular Cu(2+) detection, and a twophoton fluorescent probe for pH measurement in live cells and tissues. We conclude this Account by outlining future directions in engineering the functional surface of C-dots for a variety of in vivo imaging applications, including dots with combined targeting, imaging and therapeutic-delivery capabilities, or high-resolution multiplexed vascular imaging. With each application C-dots should open new horizons of multiplexed quantitative detection, high-resolution fluorescence imaging, and long-term, real-time monitoring of their target.
Cold pools are fundamental ingredients of deep convection. They contribute to organizing the subcloud layer and are considered key elements in triggering convective cells. It was long known that this ...could happen mechanically, through lifting by the cold pools' fronts. More recently, it has been suggested that convection could also be triggered thermodynamically, by accumulation of moisture around the edges of cold pools. A method based on Lagrangian tracking is here proposed to disentangle the signatures of both forcings and quantify their importance in a given environment. Results from a simulation of radiative‐convective equilibrium over the ocean show that parcels reach their level of free convection through a combination of both forcings, each being dominant at different stages of the ascent. Mechanical forcing is an important player in lifting parcels from the surface, whereas thermodynamic forcing reduces the inhibition encountered by parcels before they reach their level of free convection.
Key Points
Thermodynamic effect of cold pools crucial in the inhibition layer
Gust front lifting is necessary for lifting parcels from the surface
No forcing mechanism by cold pools is entirely dominant; cooperation is needed
The imbalance of Cu+ and Cu2+ in the brain is closely related to neurodegenerative diseases. However, it still lacks of effective analytical methods for simultaneously determining the concentrations ...of Cu+ and Cu2+. Herein, we created a novel SERS probe (CuSP) to real‐time track and accurately quantify extracellular concentrations of Cu+ and Cu2+ in the live brain. The present CuSP probe demonstrated specific ability for recognition of Cu+ and Cu2+ in a dual‐recognition mode. Then, a microarray consisting of 8 CuSP probes with high tempo‐spatial resolution and good accuracy was constructed for tracking and simultaneously biosensing of Cu+ and Cu2+ in the cerebral cortex of living brain. Using our powerful tool, it was found that that the concentrations of Cu2+ and Cu+ were increased by ≈4.26 and ≈1.80 times upon ischemia, respectively. Three routes were first discovered for understanding the mechanisms of the increased concentrations of Cu+ and Cu2+ during ischemia.
A novel SERS sensor was created for biosensing extracellular concentrations of Cu+ and Cu2+ simultaneously in the live brain. Using our powerful tool, three routes were discovered for understanding the mechanisms of the increased concentrations of Cu+ and Cu2+ during ischemia: Cu+ and Cu2+ were transported from neurons; Cu+ and Cu2+ were released from the destroyed copper‐containing proteins; and Cu+ was converted into Cu2+.
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