Conspectus Self-assembled nanomaterials show potential high efficiency as theranostic agents for high-performance imaging and therapy. However, superstructures and properties of preassembled ...nanomaterials are somewhat compromised under complicated physiological conditions. Given the advantages of the dynamic nature and adaptive behavior of self-assembly systems, we propose an “in vivo self-assembly” strategy for in situ construction of nanomaterials in living objects. For the proof-of-concept study of in vivo self-assembly, we developed a bispyrene (BP) molecule as a multifunctional building block. BP molecules show nonfluorescence in the monomeric state. Quantum-chemical calculations indicate that BP forms twisted intramolecular charge transfer states, which are separated into two orthogonal units, preventing the fluorescence emission. Interestingly, the typical excimeric emission of BP is observed with the formation of J-type aggregates, as confirmed by single-crystal X-ray diffraction. Packing of the BP molecules generates parallel pyrene units that interact with adjacent ones in a slipped face-to-face fashion through intermolecular π–π interactions. BP and/or its amphiphilic derivatives are capable of self-aggregating into nanoparticles (NPs) in aqueous solution because of the hydrophobic and π–π interactions of BP. Upon specific biological stimuli, BP NPs can be transformed into variable self-assembled superstructures. Importantly, the self-assembled BP NPs exhibit turn-on fluorescence signals that can be used to monitor the self-assembly/disassembly process in vitro and in vivo. On the basis of the photophysical properties of BP and its aggregates, we synthesized a series of designed BP derivatives as building blocks for in situ construction of functional nanomaterials for bioimaging and/or therapeutics. We observed several new biomedical effects, e.g., (i) the assembly/aggregation-induced retention (AIR) effect, which shows improved accumulation and retention of bioactive nanomaterials in the regions of interests; (ii) the transformation-induced surface adhesion (TISA) effect, which means the BP NPs transform into nanofibers (NFs) on cell surfaces upon binding with specific receptors, which leads to less uptake of BP NPs by cells via traditional endocytosis pathway; and (iii) transformation of the BP NPs into NFs in the tumor microenvironment, showing high accumulation and long-term retention, revealing the transformation-enhanced accumulation and retention (TEAR) effect. In this Account, we summarize the fluorescence property and emission mechanism of BP building blocks upon aggregation in the biological environment. Moreover, BP-derived compounds used for in vivo self-assembly and transformation are introduced involving modulation strategies. Subsequently, unexpected biomedical effects and applications for theranostics of BP based nanomaterials are discussed. We finally conclude with an outlook toward future developments of BP-based self-assembled nanomaterials.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract Background Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be ...accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. Objectives The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. Methods A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography–quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. Results We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). Conclusions Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In recent years, nanoscale zero-valent iron (nZVI) has been gradually applied in soil remediation due to its strong reducing ability and large specific surface area. Compared to conventional ...remediation solutions, in situ remediation using nZVI offers some unique advantages. In this review, respective merits and demerits of each approach to nZVI synthesis are summarized in detail, particularly the most commonly used aqueous-phase reduction method featuring surface modification. In order to overcome undesired oxidation and agglomeration of fresh nZVI due to its high reactivity, modifications of nZVI have been developed such as doping with transition metals, stabilization using macromolecules or surfactants, and sulfidation. Mechanisms underlying efficient removal of organic pollutants enabled by the modified nZVI lie in alleviative oxidation and agglomeration of nZVI and enhanced electron utilization efficiency. In addition to chemical modification, other assisting methods for further improving nZVI mobility and reactivity, such as electrokinetics and microbial technologies, are evaluated. The effects of different remediation technologies and soil physicochemical properties on remediation performance of nZVI are also summarized. Overall, this review offers an up-to-date comprehensive understanding of nZVI-driven soil remediation from scientific and practical perspectives.
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•Synthesized by various methods, nZVI is used to degrade organic pollutants.•Chemical and biological modifications are used to improve the activity of nZVI.•Electrokinetics, chemical, and microbial methods assist nZVI for soil remediation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lipoprotein lipase (LPL) is a rate-limiting enzyme that catalyzes hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins including chylomicrons (CM), low-density lipoproteins ...(LDL) and very low-density lipoproteins (VLDL). A variety of parenchymal cells can synthesize and secrete LPL. Recent studies have demonstrated that complicated processes are involved in LPL biosynthesis, secretion and transport. The enzyme activity of LPL is regulated by many factors, such as apolipoproteins, angiopoietins, hormones and miRNAs. In this article, we also reviewed the roles of LPL in atherosclerosis, coronary heart disease, cerebrovascular accident, Alzheimer disease and chronic lymphocytic leukemia. LPL in different tissues exerts differential physiological functions. The role of LPL in atherosclerosis is still controversial as reported in the literature. Here, we focused on the properties of LPL derived from macrophages, endothelial cells and smooth muscle cells in the vascular wall. We also explore the existence of crosstalk between LPL and those cells when the molecule mainly plays a proatherogenic role. This review will provide insightful knowledge of LPL and open new therapeutic perspectives.
•We have reviewed these complicated processes involved in biosynthesis, secretion, and transportation of LPL.•We explored the relationship of LPL and macrophages, endothelial cells, and vascular smooth muscle cells.•We reviewed its role of LPL in Atherosclerosis and other diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Many metal–organic cages (MOCs) and a few hydrogen‐bonded organic cages (HOCs) have been investigated, but little is reported about cooperative self‐assembly of MOCs and HOCs. Herein, we describe an ...unprecedented MOC&HOC co‐crystal composed of tetrahedral Ti4L6 (L=embonate) cages and in‐situ‐generated (NH3)4(TIPA)4 (TIPA=tris(4‐(1H‐1,2,4‐triazol‐1‐yl)phenyl)amine) cages. Chiral transfer is observed from the enantiopure Ti4L6 cage to enantiopure (NH3)4(TIPA)4 cage. Two homochiral supramolecular frameworks with opposite handedness (PTC‐235(Δ) and PTC‐235(Λ)) are formed. Such MOC&HOC co‐crystal features high stability in water and other solvents, affording single‐crystal‐to‐single‐crystal transformation to trap CH3CN molecules and identify disordered NH4+ cations. A tablet pressing method is developed to test the third‐order nonlinear optical property of KBr‐based PTC‐235 thin film. Such a thin film exhibits an excellent optical limiting effect.
The supramolecular self‐assembly between metal–organic cages (MOCs) and hydrogen‐bonded organic cages (HOCs) is realized in an MOC&HOC co‐crystal composed of tetrahedral Ti4L6 cages and (NH3)4(TIPA)4 cages generated in situ. The MOC&HOC co‐crystal thin film exhibits an excellent optical limiting effect.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Biltz synthesis establishes straightforward access to 5,5‐disubstituted (thio)hydantoins by combining a 1,2‐diketone and a (thio)urea. Its appealing features include inherent atom and step ...economy together with the potential to generate structurally diverse products. However, control of the stereochemistry of this reaction has proven to be a daunting challenge. Herein, we describe the first example of enantioselective catalytic Biltz synthesis which affords more than 40 thiohydantoins with high stereo‐ and regio‐control, irrespective of the symmetry of thiourea structure. A one pot synthesis of corresponding hydantoins is also documented. Remarkably, experimental studies and DFT calculations establish the reaction pathway and origin of stereoselectivity.
The first catalytic enantioselective Biltz synthesis is established, which provides a straightforward access to 5,5‐disubstituted (thio)hydantoins in high yields with excellent stereocontrol. Isotopic tracer experiments and DFT calculations reveal an exclusive 1,2‐ester shift process. The observed enantioselectivity and regioselectivity originate from 3+2 cyclization step.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Atherosclerosis has been recognized as an inflammatory disease involving the vascular wall. MicroRNAs are a group of small noncoding RNAs to regulate gene expression at the transcriptional level ...through mRNA degradation or translation repression. Recent studies suggest that miR-296 may play crucial roles in the regulation of angiogenesis, inflammatory response, cholesterol metabolism, hypertension, cellular proliferation and apoptosis. In this review, we primarily discussed the molecular targets of miR-296 involved in the development of atherosclerosis, which may provide a basis for future investigation and a better understanding of the biological functions of miR-296 in atherosclerosis.
Narrative review of ferroptosis in obesity He, Lian‐Ping; Zhou, Zi‐Xuan; Li, Cui‐Ping
Journal of cellular and molecular medicine,
April 2023, Volume:
27, Issue:
7
Journal Article
Peer reviewed
Open access
Obesity is widely recognized as a major global health problem caused by a chronic energy imbalance resulting from a combination of excess caloric intake and insufficient energy expenditure. Excessive ...energy intake and physical inactivity are traditional risk factors for obesity. Obesity is a risk factor for many diseases, including hypertension, diabetes and tumours. Recent studies have found a strong link between ferroptosis and obesity. Ferroptosis is an iron‐dependent regulated cell death caused by iron overload and reactive oxygen species‐dependent excessive accumulation of lipid peroxidation. Ferroptosis is involved in many biological processes, such as amino acid metabolism, iron metabolism and lipid metabolism. Some potential strategies to reduce the adverse effects of ferroptosis on obesity are suggested and future research priorities are highlighted.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Atherosclerotic lesions are lipometabolic disorder characterized by chronic progressive inflammation in arterial walls. Previous studies have shown that macrophage-derived lipoprotein lipase (LPL) ...might be a key factor that promotes atherosclerosis by accelerating lipid accumulation and proinflammatory cytokine secretion. Increasing evidence indicates that microRNA-27 (miR-27) has beneficial effects on lipid metabolism and inflammatory response. However, it has not been fully understood whether miR-27 affects the expression of LPL and subsequent development of atherosclerosis in apolipoprotein E knockout (apoE KO) mice. To address these questions and its potential mechanisms, oxidized low-density lipoprotein (ox-LDL)-treated THP-1 macrophages were transfected with the miR-27 mimics/inhibitors and apoE KO mice fed high-fat diet were given a tail vein injection with miR-27 agomir/antagomir, followed by exploring the potential roles of miR-27. MiR-27 agomir significantly down-regulated LPL expression in aorta and peritoneal macrophages by western blot and real-time PCR analyses. We performed LPL activity assay in the culture media and found that miR-27 reduced LPL activity. ELISA showed that miR-27 reduced inflammatory response as analyzed in vitro and in vivo experiments. Our results showed that miR-27 had an inhibitory effect on the levels of lipid both in plasma and in peritoneal macrophages of apoE KO mice as examined by HPLC. Consistently, miR-27 suppressed the expression of scavenger receptors associated with lipid uptake in ox-LDL-treated THP-1 macrophages. In addition, transfection with LPL siRNA inhibited the miR-27 inhibitor-induced lipid accumulation and proinflammatory cytokines secretion in ox-LDL-treated THP-1 macrophages. Finally, systemic treatment revealed that miR-27 decreased aortic plaque size and lipid content in apoE KO mice. The present results provide evidence that a novel antiatherogenic role of miR-27 was closely related to reducing lipid accumulation and inflammatory response via downregulation of LPL gene expression, suggesting a potential strategy to the diagnosis and treatment of atherosclerosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Perception of microbe-associated molecular patterns (MAMPs) by cell-surface-resident pattern recognition receptors (PRRs) induces rapid, robust, and selective transcriptional reprogramming, which is ...central for launching effective pattern-triggered immunity (PTI) in plants. Signal relay from PRR complexes to the nuclear transcriptional machinery via intracellular kinase cascades rapidly activates primary immune response genes. The coordinated action of gene-specific transcription factors and the general transcriptional machinery contribute to the selectivity of immune gene activation. In addition, PRR complexes and signaling components are often transcriptionally upregulated upon MAMP perception to ensure the robustness and sustainability of PTI outputs. In this review, we discuss recent advances in deciphering the signaling pathways and regulatory mechanisms that coordinately lead to timely and accurate MAMP-induced gene expression in plants.
Pathogen perception in plants leads to gene expression changes, which are critical for effective pattern-triggered immunity (PTI). Li et al. discuss recent advances in deciphering the signaling pathways and regulatory mechanisms that coordinately lead to rapid, robust, and selective transcriptional reprogramming during PTI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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