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Purely organic room-temperature phosphorescence (RTP) has attracted tremendous attention, but is rarely reported to possess stimulus responsiveness. Herein, we report a supramolecular RTP switch based on a dicationic guest molecule (BPA) and cucurbituril. BPA possesses a photosensitive 9,10-diphenylanthracene core and terminal 4-(4-bromophenyl)pyridium, which can form 1 : 4 supramolecular assembly with cucurbit[7]uril (CB[7]) and an n : n linear supramolecular polymer with cucurbit[8]uril (CB[8]). The assemblies can exhibit tunable fluorescence emission after undergoing a photoreaction of the anthracene unit in BPA. It is interesting that CB[8] can bind two bromophenylpyridinium units to form a green phosphorescent switch. Notably, the RTP of the assemblies can be reversibly switched on/off by UV irradiation or heating through a tunable Forster resonance energy transfer from 4-(4-bromophenyl)pyridium to anthracene. Moreover, the addition of cucurbituril can significantly accelerate the photoreaction rate of anthracene and enable the assembly to respond quickly to UV irradiation, which expands the application potential of this strategy in stimulus responsive RTP materials.

Five hybrid tetrapeptides, each consisting a central dipeptide segment of α-amino acid residues flanked by two aromatic γ-amino acid residues, are found to fold into well-defined β-hairpin conformations as shown by NMR, computational study, and X-ray structures. The turn loop of this β-hairpin motif accommodates different two-residue α-amino acid sequences from the highly flexible Gly-Gly, to the more restricted d -Pro-Gly. The presence of α-amino acid side chains enhances the stabilities of the β-hairpins with the exception of d -Pro-Gly-which results in destabilization. Based on this hairpin/turn motif, a variety of different dipeptide sequences of α-amino acids which rarely occur in β-turns can be introduced and presented as two-residue loops.

Naturally complete mixing promotes the spontaneous redistribution of dissolved oxygen (DO), representing an ideal state for maintaining good water quality, and conducive to the biomineralization of organic matter. Water lifting aerators (WLAs) can extend the periods of complete mixing and increase the initial mixing temperature. To evaluate the influence of artificial-induced continuously mixing on dissolved organic matter (DOM) removal performance, the variations of DOM concentrations, optical characteristic, environmental factors were studied after approaching the total mixing status via WLAs operation. During this process, the dissolved organic carbon reduced by 39.18%, whereas the permanganate index decreased by 20.47%. The optical properties indicate that the DOM became more endogenous and its molecular weight decreased. Based on the results of the Biolog EcoPlates, the microorganisms were maintained at a relatively high metabolic activity in the early stage of induced mixing when the mixing temperature was relatively high, whereas DOM declined at a high rate. With the continuous decrease in the water temperature, both the metabolic capacity and the diversity of aerobic microorganisms significantly decreased, and the rate of organic matter mineralization slowed down. The results of this study demonstrate that the artificial induced mixing largely enhanced the removal DOM performance by providing a long period of aerobic conditions and higher initial temperature.

A new type of purely organic light-harvesting phosphorescence energy transfer (PET) supramolecular assembly is constructed from 4-(4-bromophenyl)-pyridine modified β-cyclodextrin (CD-PY) as a donor, cucurbit[8]uril (CB[8]) as a mediator, rhodamine B (RhB) as an acceptor, and adamantane modified hyaluronic acid (HA-ADA) as a cancer cell targeting agent. Interestingly, the complexation of free CD-PY, which has no RTP emission in aqueous solution, with CB[8] results in the formation of CD-PY@CB[8] pseudorotaxane with an RTP emission at 510 nm. Then the addition of RhB leads to an efficient light-harvesting PET process with highly efficient energy transfer and an ultrahigh antenna effect (36.42) between CD-PY@CB[8] pseudorotaxane and RhB. Importantly, CD-PY@CB[8]@RhB assembles with HA-ADA into nanoparticles with further enhanced delayed emission at 590 nm. The nanoparticles could be successfully used for mitochondria targeted imaging in A549 cancer cells. This aqueous-state PET based on a supramolecular assembly strategy has potential application in delayed fluorescence cell imaging., A new type of purely organic light-harvesting PET supramolecular assembly is constructed with efficient energy transfer and ultrahigh antenna effect. Moreover, the assembly could be used for mitochondria targeted imaging in A549 cancer cells.

The construction of controlled biomacromolecular assemblies has become a thriving area of supramolecular chemistry. In this context, cucurbiturils (CBs), a class of macrocyclic receptors having robust skeletons, hydrophobic cavities, and carbonyl-laced portals, have been drawn into the limelight because of their advantageous molecular recognition characteristics with a variety of biomacromolecules, including peptides, nucleic acids, and proteins. In this minireview, we focus on the impressive advances in CB-based biomacromolecular assemblies, such as in biosensors and assays, the regulation of biochemical reactions, and the treatment of serious diseases. CB-promoted subcellular bioimaging has also been demonstrated in different organelles. The case studies presented herein demonstrate the numerous applications, from fundamental research to translational applications, of diverse CB-based supra/biomacromolecular architectures.

Background DAXX is a transcription repressor that has been implicated in several types of cancers, but its role in the development of gastric cancer remains unknown. Methods We analysed the expression of DAXX in 83 pairs of gastric cancer samples, including neoplastic and adjacent tissues, and correlated the expression levels with clinical stages. We also investigated the molecular mechanisms by which DAXX downregulation promotes cancer growth using both in vitro and in vivo models. Results DAXX was downregulated in advanced gastric cancer samples. The expression of DAXX inversely correlates with that of cancer stem cell markers CD44 and Oct4 in gastric cancer lines. DAXX overexpression in gastric cancer cells inhibited migration, invasion and epithelial– mesenchymal transition (EMT). The inhibition of EMT was achieved through the repression of SNAI3, a key inducer of EMT, by recruiting HDAC-1 into the nucleus. Using a xenograft mouse model, we demonstrated that the MKN45 cells formed smaller tumours when DAXX was overexpressed. Wild-type AGS cells were not able to form tumours in nude mice, but in contrast, formed visible tumours when DAXX was silenced in the cells. Conclusion We for the first time demonstrated that DAXX functions as a tumour suppressor in gastric cancer by inhibiting stem cell growth and EMT.

In this study, we have constructed a binary supramolecular nanoassembly composed of α-cyclodextrin-modified hyaluronic acid and an azobenzene-modified diphenylalanine derivative with a positively charged imidazole group. This nanoassembly can bind with siRNA through electrostatic interactions and efficiently delivered them into cancer cells and inhibited their growth.

Although purely organic room‐temperature phosphorescence (RTP) has drawn widespread attention in recent years, regulatable phosphorescence resonance energy transfer (PRET) supramolecular switch is still rare. Herein, single molecular dual‐fold supramolecular light switches, which are constructed by phenylpyridinium salts modified diarylethene derivatives (DTE‐Cn, n = 3, 5) and cucurbit[8]uril (CB[8]) are reported. Significantly, biaxial [3]pseudorotaxane displayed efficiently reversible RTP after binding with CB[8] and the phosphorescence quenching efficiency is calculated up to be 99%. Furthermore, the binary supramolecular assembly can coassemble with Cy5 to form ternary supramolecular assembly showing efficiently PRET, which is successfully applied in switchable near infrared (NIR) mitochondria‐targeted cell imaging and photocontrolled data encryption. This supramolecular strategy involving energy transfer provides a convenient approach for phosphorescent application in biology and material fields., A switchable supramolecular phosphorescence resonance energy transfer system for NIR cell imaging and data encryption is reported. This supramolecular strategy involving energy transfer provides a convenient approach for phosphorescent application in biology and material fields.

Melatonin (MEL) has been demonstrated to exert a protective effect against subarachnoid hemorrhage (SAH), and nitric oxide (NO) has been shown to play an important role in the pathogenesis of vasospasm. This study aims to explore the underlying molecular mechanisms of MEL in the control of vasospasm following SAH. MEL administration attenuates SAH-induced vasospasm and neurobehavioral deficits. Expressions of H19, eNOS, and miR-675 are low in the SAH group, while expressions of miR-138 and HIF1α are high in the SAH group. Also, MEL treatment upon SAH rats completely restores the dysregulation of H19, eNOS, miR-675, miR-138, and HIF1α to their normal levels. Moreover, MEL dose dependently increases the luciferase activity of H19 promoter and hence the expression of H19. Additionally, H19 directly targets miR-675 and miR-138 to increase miR-675 expression and inhibit miR-138 expression. As virtual target genes of miR-675 and miR-138, respectively, HIF1α and eNOS are also regulated by the treatment with MEL. In particular, MEL treatment increases the expression of miR-675 and eNOS level while decreasing the expression of miR-138 and HIF1α in a dose dependent manner. Our study found that MEL ameliorates post-SAH vasospasm by regulating the expression of eNOS and HIF1α via the H19/miR-138/eNOS/NO and H19/miR-675/HIF1α signaling pathways.

Hexavalent chromium [Cr(VI)], is a well-known toxic form of the heavy metal chromium in the natural environment. Clinical evidence has indicated that exposure to Cr(VI) can cause severe renal damage. The production of reactive oxygen species (ROS) due to intracellular reduction of Cr(VI) is the main mechanism underlying the induction of cellular dysfunction and apoptosis. The present study aimed to investigate in detail the apoptotic pathways induced by Cr(VI)-exposure in a human immortalized proximal tubular epithelial cell line HK-2, in order to understand the mechanism involved therein. Exposure to 10 µM potassium dichromate (K2Cr2O7), a toxic compound of Cr(VI), significantly decreased cell viability after 24 and 48 h of incubation and induced intracellular ROS generation. The expression levels of markers that activate the apoptotic pathway including cleaved caspase-3 and poly (ADP-ribose) polymerase were significantly upregulated in K2Cr2O7-exposed HK-2 cells. In addition, the induction of intrinsic and extrinsic apoptotic markers was detected in K2Cr2O7-exposed HK-2 cells. In summary, the present study described for the first time the novel apoptotic mechanism of Cr(VI)-toxicity in human renal cells which may be beneficial in designing optimal clinical treatment for renal damage caused by acute Cr(VI) toxicity.

Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu (RS)—a sweet plant also known as Tiancha distributed in the south of China where it is used as a beverage—recently gained extensive attention as adjuvant therapy of diabetes and hypertension. Although pharmacological studies indicate that RS has beneficial effects in regulating lipid metabolism disorder characteristics, the active chemicals responsible for this effect remains unclear. The present study aims to predict the effective substances of RS on regulating lipid metabolism disorder through the analysis of the chemical profile of RS, the absorbed prototype components in rat plasma, and network pharmacology. Also, a UPLC method able to quantify the screened potential effective chemicals of RS products was established. First, a total of 69 components—including diterpene, triterpenoids, flavonoids, polyphenols, and lignans—were systematically characterized in RS. Of those, 50 compounds were detected in the plasma of rats administered with RS extract. Through network pharmacology, 9 potential effective components, 71 target genes, and 20 pathways were predicted to be involved in RS-mediated regulation of lipid metabolism disorder. The quantitative analysis suggested that the contents of potential effective components varied among samples from different marketplaces. In conclusion, the presented results provide a chemical basis for further research of Rubus chingii var. suavissimus.

A unique fluorescent supramolecular assembly was constructed using coumarin-modified β-cyclodextrin as a reversible ratiometric probe and an adamantane-modified cyclic arginine–glycine–aspartate peptide as a cancer-targeting agent via host–guest inclusion complexation. Importantly, the coumarin-modified β-cyclodextrin not only showed higher sensitivity than the parent coumarin derivatives owing to the presence of numerous hydroxyl groups on the cyclodextrin but also provided a hydrophobic cavity for encapsulation of a cancer-targeting agent. The assembly showed a reversible and fast response to biothiols with a micromolar dissociation constant, as well as outstanding cancer cell permeability, which can be used for high-efficiency real-time monitoring of biothiols in cancer cells. This supramolecular assembly strategy endows the fluorescent probe with superior performance for dynamic sensing of biothiols., A unique fluorescent supramolecular assembly was constructed from coumarin-modified β-cyclodextrin and an adamantane-modified cyclic arginine–glycine–aspartate peptide for high-efficiency real-time monitoring of biothiols in cancer cells.

Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial–mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

Multi-color and white light luminescence materials based on supramolecular assemblies are attractive because of their potential applications in advanced light-emitting material. Herein, a cucurbit[8]uril-enhanced lanthanide luminescent supramolecular assembly was constructed in a facile but efficient way using terpyridine imidozalium cations, cucurbit[8]urils and rare earth ions such as Tb3+ and Eu3+. Significantly, the resultant fibrous supramolecular assembly, with an average width of 15 nm, could emit remarkable lanthanide luminescence, which was ten times higher than the corresponding terpyridine/Ln3+ without cucurbit[8]uril. And the solid state luminescence of supramolecular assembly could be smartly and easily turned among blue, green, red and white by adjusting the molar ratios between Tb3+ and Eu3+. The enhanced white-light emission by supramolecular strategy may provide a new approach for smart and tunable solid luminescent materials.

Intracerebral hemorrhage (ICH) is a devastating disease, and there is currently no specific pharmacological treatment that can improve clinical outcomes. Y-2 sublingual tablets, each containing 30 mg edaravone and 6 mg (+)-borneol, is undergoing a phase III clinical trial for treatment of ischemic stroke in China. The purpose of the present study is to investigate the efficacy and potential mechanism of Y-2 in a rat model of collagenase IV injection induced ICH. Sublingual administration of Y-2 at the dose of 1, 3 and 6 mg/kg improved ICH-induced sensorimotor dysfunction, alleviated cell death and histopathological change, restored the hippocampal long-term potentiation (LTP), reduced brain edema and maintained blood-brain barrier (BBB) integrality in ICH rats. Further study demonstrated that Y-2 could reduce inflammatory response and oxidative stress by decreasing the levels of myeloperoxidase (MPO), ionized calcium-binding adaptor protein-1 (Iba-1), inflammatory cytokines and oxidative products, inhibit transcription factor nuclear factor-κB (NF-κB) activation, cyclooxygenase-2 (COX-2) and matrix metallopeptidase 9 (MMP-9) expression in brain tissue around in the core regions of hematoma. Importantly, the protective efficacy of Y-2 from ICH-induced injury was superior to edaravone. In conclusion, Y-2 sublingual tablets might be a promising therapeutic agent for the treatment of ICH.

While the underlying mechanism remains unknown, Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu or Rubus suavissimus S. Lee (RS), a sweet plant distributed in southwest of China, has been used as beverage and folk medicine. Pharmacological studies indicated the potential of RS improving the obesity phenotype and hyperlipidemia. The mechanism is still not yet to be put forward. To verify the substantial effects of RS on lipid metabolism, a Syrian golden hamster model was adopted. The physiological and pathological evaluation of experimental animals demonstrated that RS can relieve the lipid metabolism disorder induced by high-fat diet and alleviated liver injury. RS upregulation the expressions of peroxisome proliferator-activated receptor α (PPARα), PPARγ and CCAAT/enhancer binding protein α (C/EBPα), as well as adipocyte-specific genes, glucose transporter 4 (Glut4), lipoprotein lipase (LPL) and fatty acid binding protein 4 (aP2). On the other side, RS suppressed the sterol regulatory element binding protein 1 (SREBP1) and downstream acetyl-CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase-1 (SCD1) and fatty acid synthase (FAS). In conclusion, RS alleviated lipid metabolism disorder symptoms caused by high-fat diet accompanied with 8 weeks of treatment, involving enhanced β-oxidation, increased adipogenesis and decreased the metabolism of fatty acids, via modulation of the PPARs/SREBP pathway in Syrian golden hamsters.

Actin cytoskeleton disruption is a promising and intriguing anticancer strategy, but their efficiency is frequently compromised by severe side effects of the actin cytoskeleton-disrupting agents. In this study, we constructed the biocompatible actin cytoskeleton-targeting multivalent supramolecular assemblies that specifically target and disrupt the tumor actin cytoskeleton for cancer therapy. The assemblies were composed of β-cyclodextrin-grafted hyaluronic acid (HACD) and iron oxide magnetic nanoparticles (MNPs) grafted by an actin-binding peptide (ABP) and adamantane (Ada)-modified polylysine. Owing to the multivalent binding between cyclodextrin and Ada, HACD, and peptide-grafted MNPs (MNP-ABP-Ada) could self-assemble to form MNP-ABP-Ada⊂HACD nanofibers in a geomagnetism-dependent manner. Furthermore, the presence of ABP rendered the assemblies to efficiently target the actin cytoskeleton. Interestingly, with the acid of a low-frequency alternating magnetic field (200 Hz), the actin cytoskeleton-targeting nanofibers could induce severe actin disruption, leading to a remarkable cell cycle arrest and drastic cell death of tumor cells both in vitro and in vivo, but showed no obvious toxicity to normal cells. The actin cytoskeleton-targeting/disrupting supramolecular assembly implies an excellent strategy for realizing efficient cancer therapy.

Supramolecular chemistry based on macrocycles such as cyclodextrins (CDs) offers the opportunity to combine synthetic motifs with naturally occurring macromolecules for the study of biological phenomena. CDs, a family of cone-shaped cyclic oligosaccharides, can selectively encapsulate various organic and inorganic molecules in their hydrophobic cavities (host–guest interactions), thereby generating reproducible, well-defined biological nanostructures with novel functionalities and environmental adaptability. In this chapter, we highlight recent work on strategies used to design and construct a diverse array of biocompatible CD-protein nanoassemblies of varying complexity. The binding characteristics of CD-based inclusion complexes are described, the responses of the complexes to chemical and physical stimuli are summarized, the principles used to design CD-based enzyme and protein mimics are discussed, and strategies for fabrication of CD-protein constructs are reviewed, with a particular focus on orthogonal host–guest complexation and ligand–receptor interactions. Such CD-protein constructs can be expected not only to allow precise manipulation of protein–protein interactions but also to provide a wealth of information about the dynamic self-assembly of biomacromolecules, which can pave the way for the development of intelligent bioinspired nanomaterials with functions that closely resemble those of naturally occurring biological materials.

MicroRNAs (miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. MicroRNA-29b (miR-29b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of miR-29b in animal and cell models by inhibiting miR-29b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg miR-29b antagomir was injected via the tail vein. MiR-29b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of miR-29b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of miR-29b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the miR-29 antagomir for 48 hours. The results revealed that miR-29b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of miR-29b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (approval No. 201709276S) on September 27, 2017.

Picrasma quassioides, a member of the Simaroubaceae family, is the subject of research in numerous pharmacological and chemical studies. This plant mainly contains alkaloids, quassinoids and terpenoids. These molecules exhibit various pharmacological benefits, such as anti-inflammatory, anticancer, and anti-viral effects, on the cardiovascular system. Alkaloids make up the majority of these molecules. This review describes 127 alkaloid substances from P. quassioides. These alkaloids can be divided into the following classes: β-carbolines, canthinones and alkaloid dimers. A compilation of their nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds and the pharmacological effects of P. quassioides are also included.

Four novel linear trinuclear manganese clusters [Mn3(Ln)2(CH3COO)4] (1, n = 1; 2, n = 2; 3, n = 3; 4, n = 4. where HL1 is 4-chloro-2-((2-(6-chloropyridin-2-yl)hydrazono)methyl)phenol, HL2 is 4-bromo-2-((2-(6-chloropyridin-2-yl)hydrazono)methyl)phenol, HL3 is 4-chloro-2-((2-(6-bromopyridin-2-yl)hydrazono)methyl)phenol, HL4 is 4-bromo-2-((2-(6-bromopyridin-2-yl) hydrazono)methyl)phenol) were synthesized through solvothermal method. Complexes 1–4 were characterized by IR, and X-ray single-crystal diffraction. Complexes 1–4 are isomorphous compounds which are trinuclear linear manganese clusters. A detailed analysis of Hirshfeld surface and 2D fingerprint plots revealed that 1–4 were supported mainly by H⋯H, H⋯X (X = Cl, Br) and O⋯H intermolecular interactions. Magnetic properties of 1–4 have been studied. In additional, complex 3 showed highly intense electrochemicaluminescence (ECL) in DMF solution.

Two new baccharane-type glycosides (1 and 2), together with seven known baccharane-type glycosides (3―9) hosenkoside A, hosenkoside B, hosenkoside C, hosenkoside F, hosenkoside M, hosenkoside K and hosenkoside G were isolated from the dried seeds of Impatientis balsamina L. The new baccharane-type glycosides were identified as honsenkol A-3-O-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl-O-β-D-glucopyranosyl(1) and (3S,4R,17R,20S)-17-hydroxy-3-O-β-D-xylopyranose(12)-β-D-glucopyranosyl-26-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl-21,24-epoxybaccharane(2), respectively, by spectroscopic methods, including NMR(1D and 2D), IR and HR-ESI-MS. Compounds 1 and 2 were evaluated for in vitro inhibitory activity against the cell lines. Compound 2 with a new baccharane skeleton had anti-hepatic fibrosis activity against A375 cells in bioassay results, which means the new compounds have potential value in antitumor applications.

The ratio of intercellular to ambient CO2 concentrations (c i/c a) plays a key role in ecophysiology, micrometeorology, and global climatic change. However, systematic investigation on c i/c a variation and its determinants are rare. Here, the c i/c a was derived from measuring ecosystem fluxes in an even-aged monoculture of rubber trees (Hevea brasiliensis). We tested whether c i/c a is constant across environmental gradients and if not, which dominant factors control c i/c a variations. Evidence indicates that c i/c a is not a constant. The c i/c a exhibits a clear "V"-shaped diurnal pattern and varies across the environmental gradient. Water vapor pressure deficit (D) is the dominant factor controls over the c i/c a variations. c i/c a consistently decreases with increasing D. c i/c a decreases with square root of D as predicted by the optimal stomatal model. The D-driving single-variable model could simulate c i/c a as well as that of sophisticated model. Many variables function on longer timescales than a daily cycle, such as soil water content, could improve c i/c a model prediction ability. Ecosystem flux can be effectively used to calculate c i/c a and use it to better understand various natural cycles.

Isoindoline nitroxide-containing porphyrins were synthesized by the reaction of 5-phenyldipyrromethane and 5-(4′-nitrophenyl)-dipyrromethane with 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl using the Lindsey method. These spin-labeled porphyrins were further characterized by MS, UV, FTIR, 1H-NMR, cyclic voltammetry, electron paramagnetic resonance (EPR), and fluorescence spectroscopy. The electrochemical assay demonstrated that these isoindoline nitroxides-containing porphyrins had similar electrochemical and redox properties as 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl. Electron paramagnetic resonance test exhibited these porphyrins possessed the hyperfine splittings and characteristic spectra of isoindoline nitroxides, with typical nitroxide g-values and nitrogen isotropic hyperfine coupling constants. Fluorescence spectroscopy revealed that these porphyrins indicated fluorescence suppression characteristic of nitroxide–fluorophore systems. Moreover, their reduced isoindoline nitroxide-containing porphyrins eliminated the fluorescence suppression and displayed strong fluorescence. Thus, these isoindoline nitroxide-containing porphyrins may be considered as the potential fluorescent and EPR probes.

Supramolecular encapsulation has been developed into a powerful tool in clearance of toxic substances and hazardous waste from living body and external environments. Herein we tested the special efficacy of tyramine-modified β-cyclodextrin (1) in inhibiting and reversing of the inherent cytotoxicity of deoxycholic acid (DCA). The decarboxylation from tyrosine to tyramine in 1 is crucial to the mutual electrostatic communication, ultimately leading to great enhancement in binding affinity and molecular selectivity toward bile acids. As a result, the DCA-mediated cytotoxicity could be largely eliminated by the biocompatible 1. Meanwhile, the excess DCA could be rapidly excreted by 1 via rat urinary clearance, thus facilitating the decrease of DCA concentration in blood. This study presents a proof of principle that the supramolecular encapsulation with functional cyclodextrin derivatives can efficiently modulate the cell progression and remove the cytotoxic DCA, which provides a practical approach to prevent or treat bile acid-involved diseases.

While angiotensin II (ang II) has been implicated in the pathogenesis of cardiac cachexia (CC), the molecules that mediate ang II's wasting effect have not been identified. It is known TNF-α level is increased in patients with CC, and TNF-α release is triggered by ang II. We therefore hypothesized that ang II induced muscle wasting is mediated by TNF-α. Ang II infusion led to skeletal muscle wasting in wild type (WT) but not in TNF alpha type 1 receptor knockout (TNFR1KO) mice, suggesting that ang II induced muscle loss is mediated by TNF-α through its type 1 receptor. Microarray analysis identified cholesterol 25-hydroxylase (Ch25h) as the down stream target of TNF-α. Intraperitoneal injection of 25-hydroxycholesterol (25-OHC), the product of Ch25h, resulted in muscle loss in C57BL/6 mice, accompanied by increased expression of atrogin-1, MuRF1 and suppression of IGF-1/Akt signaling pathway. The identification of 25-OHC as an inducer of muscle wasting has implications for the development of specific treatment strategies in preventing muscle loss., Graphical abstract Image 1, Highlights • Ang II induced muscle wasting is mediated by TNF-α, which in turn up regulates Ch25h • Knockout of TNFR1 inhibits the production of 25-OHC and blocks ang II induced muscle loss in mice • 25-OHC injection induces muscle wasting in mice by activating GSK3β • A GSK3β inhibitor blocks ang II induced muscle atrophy, which paves the way for targeted therapy to treat muscle wasting Cardiac cachexia (CC), a condition characterized by weight loss and muscle wasting, is a serious complication that occurs in patients with chronic heart failure. This condition impairs patient's daily physical activity and their quality of life. Specific therapy for CC is currently unavailable because the pathogenesis remains unknown. Previous studies have identified angiotensin II (ang II) as an important mediator of CC. We now report a previously unrecognized role of 25-hydroxycholesterol (25-OHC) in mediating ang II induced muscle loss. The identification of 25-OHC as a muscle wasting inducer has implications for the development of therapeutic intervention in preserving muscle mass.

A combined proteomic and metabonomic approach was used to investigate the metabolism of Lactococcus lactis ssp. lactis subjected to glucose stress treatment. A proteomic method was used to determine 1,427 altered proteins, including 278 proteins with increased expression and 255 proteins with decreased expression. A metabonomic approach was adopted to identify 98 altered metabolites, including 62 metabolites with increased expression and 26 metabolites with decreased expression. The integrated analysis indicated that the RNA and DNA mismatch repair process and energy metabolism were enhanced in response to high-glucose stress in L. lactis. Lactococcus lactis responded to glucose stress by up-regulating oxidoreductase activity, which acted on glycosyl bonds, hydrolase activity, and organic acid transmembrane transporter activity. This led to an improvement in the metabolic flux from glucose to pyruvate, lactate, acetate, and maltose. Down-regulation of amino acid transmembrane transporter, aminoacyl-transfer RNA ligase, hydroxymethyl-, formyl-, and related transferase activities resulted in a decrease in the nitrogen metabolism-associated metabolic pathway, which might be related to inhibition of the production of biogenic amines. Overall, we highlight the response of metabolism to glucose stress and provide potential possibilities for the reduced formation of biogenic amines in improved level of sugar in the dairy fermentation industry. Moreover, according to the demand for industrial production, sugar concentration in fermented foods should be higher, or lower, than a set value that is dependent on bacterial strain and biogenic amine yield.

Chromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However, the optimal regimen and protective mechanisms of NAC are not fully understood in human renal cells. Our results showed that exposure to 10 &mu, M K2Cr2O7, a toxic Cr(VI) compound, induced apoptosis and production of intracellular ROS in the human proximal tubular epithelial cell line HK-2. Supplements of 600 or 1000 &micro, g/mL NAC inhibited intracellular ROS in HK-2 cells exposed to Cr(VI) and significantly increased cell viability within 2 h of Cr(VI)-induced cytotoxicity. Moreover, Cr(VI) induced the expression of apoptosis markers, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, cleaved-caspase 8, and cleaved-caspase 9, and altered the expression ratio of Bax/Bcl-xL. Expression of apoptosis markers within 2 h of Cr(VI)-induced cytotoxicity in cells treated with 600 &micro, g/mL NAC was significantly suppressed. However, delayed treatment with NAC at 4 h and 8 h after exposure to Cr did not suppress the activation of apoptotic pathways. In summary, our study reports the optimum timing and dose of NAC for the protection of human renal proximal tubular cells from Cr(VI)-induced cell death. The NAC treatment strategy described could be applied in clinical practice to suppress renal cell apoptosis, which in turn could rescue renal function.

To investigate the possibly carcinogenic substance occurring in soy sauce, the furan, 5-hydroxymethylfurfural (HMF) and nitrite, as well as chemical properties, such as total titratable acid, reducing sugars, ethanol, amino nitrogen and total nitrogen, analysis in sixteen commercial soy sauce from the China market were determined using chromatography-mass spectrometry method. There were considerable variations in furan, HMF and nitrite concentrations of different commercial soy sauces. The results showed that the level of furan and 5-hydroxymethylfurfural of the soy sauce studied ranges from15.36 to 119.82 µg/kg and 0.21 to 4.27 mg/kg, respectively, whereas the content of nitrite ranges from 0.04 to 0.73 mg/kg. The results indicated that the level of nitrogen and glucose may have a relationship with formation of furan, 5-HMF and nitrite in soy sauce. It was observed that soy sauce may be an important source of contamination by furan, HMF and nitrite.

A new flavonoid diglycoside named buxusoside (1), together with its aglycone chrysosplenol-D (2), as well as 4’, 5-dihydroxy-3,6,7-trimethoxyflavone (3) and 3’,4’,5-trihydroxy-3,6,7-trimethoxyflavone (4), were isolated from the 70% EtOH extract of the air-dried plant of Buxus sinica. Its structure was elucidated mainly by 1D and 2D NMR spectra.

Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. To learn more, Dasm1 knockout mice were constructed and employed to confirm that Dasm1 regulates dendrite arborization and spine formation in vivo. We performed a yeast two-hybrid screen using Dasm1, revealing MRCKβ as a putative partner; additional lines of evidence confirmed this interaction and identified cytoplasmic proline-rich region (823-947 aa) of Dasm1 and MRCKβ self-activated kinase domain (CC1, 410-744 aa) as necessary and sufficient for binding. Using co-immunoprecipitation assay, auto-phosphorylation assay and BS3 cross-linking assay, we show that Dasm1 binding triggers a change in MRCKβ's conformation and subsequent dimerization, resulting in auto-phosphorylation and activation. Activated MRCKβ in turn phosphorylates a class 2 regulatory myosin light chain (MLC2), which leads to enhanced actin rearrangement, causing the dendrite outgrowth and spine formation observed before. Removal of Dasm1 in mice leads to behavioral abnormalities. Together, these results reveal a crucial molecular pathway mediating cell surface and intracellular signaling communication to regulate actin dynamics and neuronal development in the mammalian brain.

Graphene nanosheets (GS) were easily prepared through liquid-phase exfoliation of graphite powder in N , N -dimethylformamide (DMF) with the assistance of sodium citrate. Then, GS was coated onto a glassy carbon electrode (GCE) surface by drop to fabricate a GS/GCE nanointerface. Subsequently, by using tetraethylorthosilicate sol as precursor, nanosilica was electrochemically deposited onto the GS/GCE surface to produce a nanocomposite film electrode (nanosilica/GS/GCE). Electrochemical behaviors of methyl parathion (MP) on the nanosilica/GS/GCE surface were investigated thoroughly. It was found that the nanosilica/GS nanocomposites can improve the redox peak currents of MP significantly due to the synergetic effect. The oxidation peak current was linearly related to MP concentration in the range from 0.0005 μmol/L to 5.6 μmol/L. The detection limit was calculated to be 0.07 nmol/L (S/N = 3). The developed method was used to determine MP in real samples. The recoveries were in the range from 95.4% to 104.2%, demonstrating satisfactory results.

Purpose To investigate the in vitro effect of short interfering RNAs (siRNAs) against Nogo receptor (NgR) on neurite outgrowth under an inhibitory substrate of central nervous system (CNS) myelin. Methods Three siRNA sequences against NgR were designed and transfected into cerebellar granule cells (CGCs) to screen for the most efficient sequence of NgR siRNA by using reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. NgR siRNA sequence 1 was found the most efficient which was then transfected into the CGCs grown on CNS myelin substrate to observe its disinhibition for neurite outgrowth. Results Compared with the scrambled control sequence of siRNA, the NgR siRNA sequence 1 significantly decreased NgR mRNA level at 24 h and 48 h (p

Except for few symptoms-improved drugs for Alzheimer's disease (AD), no disease-modified drug has been developed, especially for AD in type 2 diabetes mellitus (T2DM). SCR-1693, a disease-mortified candidate for AD, which is now in Phase I clinical study in China, improves Aβ25-35-impaired cognitive function in rodent's models. Here we report the effect of SCR-1693 on regulation of tau phosphorylation and insulin resistance associated cognition, and illustrate its underlying mechanism. We found that in intracerebroventricular injection of streptozotcin (STZ) rats, oral administration of SCR-1693 dose-dependently improved the learning and memory in Morris water maze test, decreased tau hyperphosphorylation, astrogliosis and postsynaptic protein loss in hippocampus. In Neura-2a cells with stable transfection of full-length human tau (Neura-2a-tau), treatment of SCR-1693 concentration-dependently enhanced the activation of protein phosphatase (PP1) and protein phosphatase 2A (PP2A), decreased cellular tau phosphorylation, and increased insulin-induced cellular signaling to reverse insulin resistance. Pre-treatment with the inhibitor of PP1 and PP2A inhibited the effect of SCR-1693 on both of tau phosphorylation and insulin signaling in Neura-2a-tau cells. All data suggest that an increase of activity of tau phosphatase was involved in the mechanism of SCR-1693 on the regulation of tau phosphorylation and insulin signaling, and SCR-1693 is considerable candidate for insulin resistance associated sporadic AD.

Cyclodextrins (CDs), which are a class of cyclic oligosaccharides extracted from the enzymatic degradation of starch, are often utilized in molecular recognition and assembly constructs, primarily via host-guest interactions in water. In this review, recent progress in CD-based supramolecular nanoassemblies that are sensitive to chemical, biological, and physical stimuli is updated and reviewed, and intriguing examples of the biological functions of these nanoassemblies are presented, including pH- and redox-responsive drug and gene delivery, enzyme-activated specific cargo release, photoswitchable morphological interconversion, microtubular aggregation, and cell-cell communication, as well as a geomagnetism-controlled nanosystem for the suppression of tumor invasion and metastasis. Moreover, future perspectives and challenges in the fabrication of intelligent CD-based biofunctional materials are also discussed at the end of this review, which is expected to promote the translational development of these nanomaterials in the biomedical field.

Benzyl isothiocyanate (BITC), a component of dietary food, possesses a powerful anticancer activity. Previous studies have shown that BITC produces a large number of intracellular reactive oxygen species (ROS) and increases intracellular Ca2+ release from endoplasmic reticulum (ER), leading to the activation of the apoptotic mechanism in tumor cells. However, there is not much known regarding the inhibitory effect of BITC on cisplatin-resistant oral cancer cells. The purpose of this study was to examine the anticancer effect and molecular mechanism of BITC on human cisplatin-resistant oral cancer CAR cells. Our results demonstrated that BITC significantly reduced cell viability of CAR cells in a concentration- and time-dependent manner. BITC was found to cause apoptotic cell shrinkage and DNA fragmentation by morphologic observation and TUNEL/DAPI staining. Pretreatment of cells with a specific inhibitor of pan-caspase significantly reduced cell death caused by BITC. Colorimetric assay analyses also showed that the activities of caspase-3 and caspase-9 were elevated in BITC-treated CAR cells. An increase in ROS production and loss of mitochondria membrane potential (ΔΨm) occurred due to BITC exposure and was observed via flow cytometric analysis. Western blotting analyses demonstrated that the protein levels of Bax, Bad, cytochrome c, and cleaved caspase-3 were up-regulated, while those of Bcl-2, Bcl-xL and pro-caspase-9 were down-regulated in CAR cells after BITC challenge. In sum, the mitochondria-dependent pathway might contribute to BITC-induced apoptosis in human cisplatin-resistant oral cancer CAR cells.

RUNX1 is a transcription factor that is not expressed in uninjured muscles, but can be detected in denervated muscles, suggesting a role of RUNX1 in muscle's response to injury. However, the role of RUNX1 in muscle's response to ischemia has not been reported. Our study showed that Runx1 is up regulated in skeletal muscle during ischemia reperfusion induced injury. Over-expression of Runx1 in C2C12 cells inhibits myogenic differentiation, but promotes proliferation of myoblasts. Consistent with these findings, we found that Runx1 expression was decreased in differentiated satellite cells. Our results indicate that Runx1 regulates muscle regeneration by promoting proliferation of satellite cells.

Nickel coated Zr-V-Fe non-evaporable getter (NEG) powders were prepared using electroless plating. The microstructure and composition of the Ni-coated Zr-V-Fe powders were analyzed by XRD, SEM and EDS. The hydrogen absorption performance of Ni-coated Zr-V-Fe powders and as-prepared powders were analyzed by dynamic method after an activation at 300°C for 2 hours. The hydrogen absorption performance of Ni-coated Zr-V-Fe powders and as-prepared powders at 100°C, 200°C, 300°C, 400°C, and 500°C were also analyzed. The results indicated that Ni existed as crystalline phase. The Ni coating played an important role as a catalyst which favored the dissociation of hydrogen on surface and Ni lowers the hydrogen diffusion energy for the Zr-V-Fe powders. The hydrogen absorption kinetics of Ni-coated Zr-V-Fe powders was improved in comparison with that of the as-prepared powders, and a relatively higher absorption rate was exhibited.

Liver diseases are one of the leading causes of death in the world. In spite of tremendous advances in modern drug research, effective and safe hepatoprotective agents are still in urgent demand. Natural products are undoubtedly valuable sources for drug leads. A number of natural triterpenoids were reported to possess pronounced hepatoprotective effects, and triterpenoids have become one of the most important classes of natural products for hepatoprotective agents. However, the significance of natural triterpenoids has been underestimated in the hepatoprotective drug discovery, with only very limited triterpenoids being covered in the reviews of hepatoprotective natural products. In this paper, ca 350 natural triterpenoids with reported hepatoprotective effects in ca 120 references between 1975 and 2016 will be reviewed, and the structure-activity relationships of certain types of natural triterpenoids, if available, will be discussed. Patents are not included.

Objective Gadolinium diethylenetriaminepentaacetic di[5-(4'-amidophenyl)-10,15,20- tris(4'-sulfonatophenyl) porphyrin trisodium salt] (Gd-DTPA-2APTSPP) was synthesized by the reaction of diethylenetriaminepentaacetic dianhydride with 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin and subsequently chelation with gadolium chloride. Methods This gadolinium complex was characterized and its properties in vitro and in vivo were also evaluated. Compared with Gd-DTPA, Gd-DTPA-2APTSPP possessed high relaxivity r1, low cytotoxicity to HeLa cells and high enhanced signal intensities of the VX2 carcinoma in rabbits for a prolonged time. Conclusion Moreover, Gd-DTPA-2APTSPP can distinguish the VX2 carcinoma from the reactive hyperplasia incited by inflammation and normal tissues in rabbits. Therefore, Gd-DTPA-2APTSPP can be taken up selectively by tumors and show the potential as a tumor-targeting MRI contrast agent.

Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals.

The objective of this study was to determine the effect fresh celery powder and starter culture (FCP+SC), blanching celery powder and starter culture (BCP+SC) had on the quality characteristics of indirectly cured sausages, Two treatments (TRT) (TRT 1: FCP+SC, 0.3%FCP+0.033%WBL-45; TRT 2: BCP+SC, 0.3%BCP+0.033%WBL-45 ), Negative Control (NC) (no-nitrite-added control), Positive Control (PC) (0.1%sodium nitrite-added control) were investigated. Residual nitrite levels throughout storage is always higher in PC than FCP+SC and BCP+SC(P< 0.05), but in TBARS, PC is better than FCP+SC and BCP+SC(P< 0.05). Few differences existed between TRTs and PC for a* and gel strength. The processing methods investigated to manufacture “naturally cured” in this study were applied for products instead of sodium nitrite.

This paper describes the kilogram-scale regioselective synthesis of various fluorinated arylboronic acids, aryl iodides, aryl acids, aryl aldehydes, and cyclohexenyl-substituted aryls in good to hi...

The objective of this study was to evaluate the use of high pressure processing (HPP) as a preservation method of meat products. Vacuum-packaged fish patties were subjected to HPP (300 MPa for 30 min 15°C or 500 Mpa for 10 min at 15°C). Untreated samples represented the control group. The three groups were stored at 4°C for 0–5 weeks. Color parameters, pH, thiobarbituric (TBARS), bacterial growth, and Oxidation-Reduction Potential (ORP) were determined. The results revealed that the 500-MPa treatment inhibited bacterial growth and extended the shelf-life of fish patties to four weeks with insignificant effects on the physicochemical attributes.