Nitric oxide (NO) is an important signaling molecule in biology. Both NO excess and insufficiency have been implicated in numerous physiological and pathological conditions. In order to study the ...diverse biological roles of NO in cells and tissues, many techniques have been developed for assaying NO. Recently, new generations of fluorescent probes have become indispensible tools for the study of NO biology because of their sensitivity, selectivity, spatiotemporal resolution, and experimental feasibility. Rational application of these probes in the study requires the understanding of the molecular mechanism that the probes are involved in. In this review, we will present an arsenal of fluorescent probes used to detect NO in living cells and animal tissues. We will also discuss the molecular mechanisms, actualities and prospects of fluorescent probes in detecting NO in cell biology.
This tutorial review presents an arsenal of fluorescent probes used to detect NO in living cells and animal tissues.
Due to inherently poor healable and stretchable features, the most explored polyvinyl alcohol-based gel electrolytes cannot well meet the requirements of stretchable, healable and multifunctional ...supercapacitors. Here, we report a hydrogel of a copolymer cross-linked by double linkers of Laponite (synthetic hectorite-type clay) and graphene oxide. The resultant hydrogel shows high mechanical stretchability, excellent ionic conductivity, and superior healable performance. Along with designing wrinkled-structure electrodes, supercapacitors fabricated by using this hydrogel as a gel electrolyte not only exhibit ultrahigh mechanical stretchability of 1000%, but also achieve repeated healable performance under treatments of both infrared light irradiation and heating. More significantly, a broken/healed supercapacitor also possesses an ultrahigh stretchability up to 900% with slight performance decay. This hydrogel electrolyte could be easily functionalized by introducing other functional components, and extended for use in other portable and wearable energy related devices with multifunction.
The microscale composite structure strategy of embedding CsPbBr3 nanocrystals (NCs) in the microscale Cs4PbBr6 matrix (CPB113/CPB416) has successfully demonstrated its ability to resolve the ...fluorescence quenching of perovskite NCs in the solid agglomeration state due to the loss of quantum confinement. Unfortunately, the controllable synthesis of monodisperse nanoscale composites with bright emission in the solid state remains a great challenge. Here, we present for the first time a novel supersaturated recrystallization process to controllably synthesize monodisperse CPB113/CPB416 composite NCs with bright emission in the solid form, where CsPbBr3 NCs were uniformly embedded in the nano hexagonal Cs4PbBr6 matrix. The existence of 2-methylimidazole (MeIm) not only can control the composition rate of CsPbBr3 to Cs4PbBr6, the size and dispersity of CsPbBr3 in the composite NCs but can also help controllably obtain the monodisperse and hexagonal Cs4PbBr6 matrix. The as-prepared composite structure can effectively prevent CsPbBr3 fluorescence quenching and make the composite NCs have a high photoluminescence quantum yield (PLQY) of 83%. In addition, we obtained tunable blue to red emitting composite NCs by varying the halide salts.
This work designs an experimental model of tight sandstone with a closed cemented pre-existing fracture network (CCPF) to explore the influence of closed cemented natural fractures on the propagation ...behavior of hydraulic fracture (HF) in tight sandstone formations. The influence of CCPFs with different directions on the initiation, deflection, and propagation of HF is studied based on tri-axial hydraulic fracturing experiments with acoustic emission (AE) monitoring technology. The experimental results show four types of interaction behavior between HFs and CCPFs: deflection I; deflection II; penetration; and composite pattern. When the angle (α) between the HFs and CCPF is 0° ± 15°, their interaction is deflection I. During the process of hydraulic fracturing, the CCPF open with few AE events. When α = 90° ± 15°, the interaction between the HF and CCPFs includes deflection II and penetration patterns. The HF mainly extends in the rock matrix and is accompanied by significant AE events. When α = 45° ± 15°, the interaction is complicated and includes composite and deflection I patterns. The accumulated AE energy of composite interaction pattern shows a ladder-type increase. Under the same in-situ stress conditions, the HF geometry is the most complicated with the largest number of communicated natural fractures when the angle between the maximum principal horizontal stress direction and CCPF is 30°–60°. The experimental model designed in this paper can reproduce the complex propagation patterns of HFs in fractured tight sandstone formations, and the results provide a reliable basis for follow-up theoretical studies and engineering applications.
•A new experimental model of fractured tight sandstone formation is established which includes several groups of cemented closed fractures in different directions.•The complex fracture propagation patterns revealed the physical experiment of hydraulic fracturing combing the AE monitoring technology.•The relationship between the characteristics of injection pressure curve and fracture propagation patterns was explored.•Findings about the propagation mechanism of hydraulic fracture under the influence of closed cemented fracture was discussed.
The objective of this study was to evaluate the in vitro antioxidant activity of high molecular weight chitosan based films. Three kinds of water-soluble quaternized chitosans with high molecular ...weight, namely N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (400-HTCC and 1240-HTCC), N-(2-hydroxyl) propyl-3-triethyl ammonium chitosan chloride (400-HTEC and 1240-HTEC), and O-(2-hydroxyl) propyl-3- trimethyl ammonium chitosan chloride (400-O-HTCC) were prepared from high molecular weight chitosans (400 and 1240 kDa). The in vitro antioxidant activity of a high molecular weight chitosan (1240-CS) and five quaternized chitosans was evaluated and compared as radical scavengers against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH•), hydroxyl radical (•OH), and superoxide radical (•O2 –) using established methods, and the effect of the molecular weight, the concentration, the newly generated hydroxyl group, the extra introduced positive charge of quaternary ammonium salt group, etc., on the antioxidant activity of these high molecular weight chitosans is discussed. The data obtained in vitro models exhibited good antioxidant potency and suggested the possibility that high molecular weight chitosan based films could be effectively employed as natural antioxidant materials for application in the field of food and medicine.
Nanoscaled light-triggered nitric oxide (NO) delivery vehicles with the ability of near-infrared (NIR) fluorescence imaging was presented, which consisted of chitosan (CS)-based S-nitrosothiols (SNO) ...and encapsulated silver sulfide quantum dots (Ag2S QDs). CS-SNO compounds that bore NO-storing functional groups were prepared via amino modification of chitosan. Water-soluble Ag2S QDs were synthesized and conjugated with the CS-SNO compounds with the aid of ethylenediaminetetraacetic acid (EDTA). The biocompatible Ag2S-CS-SNO nanospheres, with dimension of ∼117 nm, exhibited bright NIR fluorescence and satisfactory photostability under NIR irradiation. The Ag2S-CS-SNO nanospheres could release NO under irradiation of UV or visible light at physiological pH and temperature yet would hardly release NO if NIR irradiation was applied. Cell imaging was successfully performed, demonstrating that the Ag2S-CS-SNO nanospheres could emit readily observable NIR fluorescence and release NO in living cells. The NIR fluorescence imaging of the Ag2S-CS-SNO nanospheres did not interfere with the light-triggered NO release from them, which would provide new perspectives for the application of multifunctional nanostructured materials in diagnostics and imaging.
Triple-negative breast cancer (TNBC) is treated with cytotoxic chemotherapy and is often characterized by early relapse and metastasis. To form a secondary (recurrent and/or metastatic) tumor, a ...breast cancer cell must evade the innate and adaptive immune systems. CD47 enables cancer cells to evade killing by macrophages, whereas CD73 and PDL1 mediate independent mechanisms of evasion of cytotoxic T lymphocytes. Here, we report that treatment of human or murine TNBC cells with carboplatin, doxorubicin, gemcitabine, or paclitaxel induces the coordinate transcriptional induction of CD47, CD73, and PDL1 mRNA and protein expression, leading to a marked increase in the percentage of CD47⁺CD73⁺PDL1⁺ breast cancer cells. Genetic or pharmacological inhibition of hypoxia-inducible factors (HIFs) blocked chemotherapy-induced enrichment of CD47⁺CD73⁺PDL1⁺ TNBC cells, which were also enriched in the absence of chemotherapy by incubation under hypoxic conditions, leading to T cell anergy or death. Treatment of mice with cytotoxic chemotherapy markedly increased the intratumoral ratio of regulatory/effector T cells, an effect that was abrogated by HIF inhibition. Our results delineate an HIF-dependent transcriptional mechanism contributing to TNBC progression and suggest that combining chemotherapy with an HIF inhibitor may prevent countertherapeutic induction of proteins that mediate evasion of innate and adaptive antitumor immunity.
In this review on the exploration and development process of the Shunbei ultra-deep carbonate oil and gas field in the Tarim Basin, the progress of exploration and development technologies during the ...National 13th Five-Year Plan of China has been summarized systematically, giving important guidance for the exploration and development of ultra-deep marine carbonate reservoirs in China and abroad. Through analyzing the primary geological factors of “hydrocarbon generation-reservoir formation-hydrocarbon accumulation” of ancient and superposed basin comprehensively and dynamically, we point out that because the Lower Cambrian Yuertusi Formation high-quality source rocks have been located in a low-temperature environment for a long time, they were capable of generating hydrocarbon continuously in late stage, providing ideal geological conditions for massive liquid hydrocarbon accumulation in ultra-deep layers. In addition, strike-slip faults developed in tectonically stable areas have strong control on reservoir formation and hydrocarbon accumulation in this region. With these understandings, the exploration focus shifted from the two paleo-uplifts located in the north and the south to the Shuntuoguole lower uplift located in between and achieved major hydrocarbon discoveries. Through continuing improvement of seismic exploration technologies for ultra-deep carbonates in desert, integrated technologies including seismic acquisition in ultra-deep carbonates, seismic imaging of strike-slip faults and the associated cavity-fracture systems, detailed structural interpretation of strike-slip faults, characterization and quantitative description of fault-controlled cavities and fractures, description of fault-controlled traps and target optimization have been established. Geology-engineering integration including well trajectory optimization, high efficiency drilling, completion and reservoir reformation technologies has provided important support for exploration and development of the Shunbei oil and gas field.
Chemokines are a group of cytokines that play important roles in cell migration, inflammation, and immune defense. In this study, we identified a CXC chemokine, CXCL10, from Japanese flounder
...Paralichthys olivaceus
(named PoCXCL10) and investigated its immune function. Structurally, PoCXCL10 possesses an N-terminal coil, three β-strands, and a C-terminal α-helix with cationic and amphipathic properties. PoCXCL10 expression occurred in multiple tissues and was upregulated by bacterial pathogens. Recombinant PoCXCL10 (rPoCXCL10) promoted the migration, cytokine expression, and phagocytosis of flounder peripheral blood leukocytes (PBLs). rPoCXCL10 bound to and inhibited the growth of a variety of common Gram-negative and Gram-positive fish pathogens. rPoCXCL10 killed the pathogens by causing bacterial membrane permeabilization and structure destruction. When introduced
in vivo
, rPoCXCL10 significantly inhibited bacterial dissemination in fish tissues. A peptide derived from the C-terminal α-helix exhibited bactericidal activity and competed with rPoCXCL10 for bacterial binding. Deletion of the α-helix affected the
in vitro
bactericidal activity but not the chemotaxis or
in vivo
antimicrobial activity of PoCXCL10. Together, these results indicate that PoCXCL10 exerts the role of both an immunoregulator and a bactericide/bacteriostatic
via
different structural domains. These findings provide new insights into the immune function and working mechanism of fish CXC chemokines.
Abstract Coordination of neuronal differentiation with expansion of the neuroepithelial/neural progenitor cell (NEPC/NPC) pool is essential in early brain development. Our in vitro and in vivo ...studies identify independent and opposing roles for two neural-specific and differentially expressed non-coding RNAs derived from the same locus: the evolutionarily conserved lncRNA Rncr3 and the embedded microRNA miR124a-1 . Rncr3 regulates NEPC/NPC proliferation and controls the biogenesis of miR124a , which determines neuronal differentiation. Rncr3 conserved exons 2/3 are cytosine methylated and bound by methyl-CpG binding protein MeCP2, which restricts expression of miR124a embedded in exon 4 to prevent premature neuronal differentiation, and to orchestrate proper brain growth. MeCP2 directly binds cytosine-methylated Rncr3 through previously unrecognized lysine residues and suppresses miR124a processing by recruiting PTBP1 to block access of DROSHA-DGCR8. Thus, miRNA processing is controlled by lncRNA m 5 C methylation along with the defined m 5 C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.
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