Construction of a New Probe Based on Copper Chaperone Protein for Detecting Cu2+ in Cells.

Biomacromolecular probes have been extensively employed in the detection of metal ions for their prominent biocompatibility, water solubility, high selectivity, and easy modification of fluorescent groups. In this study, a fluorescent probe FP was constructed. The probe FP exhibited high specificity recognition for Cu2+. With the combination of Cu2+, the probe was subjected to fluorescence quenching. The research suggested that the probe FP carried out the highly sensitive detection of Cu2+ with detection limits of 1.7 nM. The fluorescence quenching of fluorescamine was induced by Cu2+ perhaps due to the PET (photoinduced electron transfer) mechanism. The FP-Cu2+ complex shows weak fluorescence, which is likely due to the PET quenching effect from Cu2+ to fluorescamine fluorophore. Moreover, the probe FP can be employed for imaging Cu2+ in living cells. The new fluorescent probe developed in this study shows the advantages of good biocompatibility and low cytotoxicity. It can be adopted for the targeted detection of Cu2+ in cells, and it has promising applications in the mechanism research and diagnosis of Cu2+-associated diseases.

A multi-wavelength cross-reactive fluorescent sensor ensemble for fingerprinting flavonoids in serum and urine.

Flavonoids are a kind of natural polyphenols which are closely related to human health, and the identification of flavonoids with similar structures is an important but difficult issue. We herein easily constructed a powerful fluorescent sensor ensemble by using surfactant cetyltrimethylammoniumbromide (CTAB) encapsulating two commercially available fluorescent probes (F1 and F2) with multi-wavelength emission. Fluorescence measurements illustrate the present sensor ensemble exhibits turn-off responses to flavones and flavonols but ratiometric responses to isoflavones, owing to different FRET processes. The heat map and linear discriminant analysis (LDA) results show that this single sensor can effectively distinguish 6 flavonoids belong to three subgroups by collecting the fluorescence variation at four typical wavelengths. Moreover, it can be applied to identify different flavonoids even in biofluids like serum and urine, providing potential practical application.

Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study.

Astragalus membranaceus has complex components as a natural drug and has multilevel, multitarget, and multichannel effects on dilated cardiomyopathy (DCM). However, the immune mechanism, gene module, and molecular subtype of astragalus membranaceus in the treatment of DCM are still not revealed. Microarray information of GSE84796 was downloaded from the GEO database, including RNA sequencing data of seven normal cardiac tissues and ten DCM cardiac tissues. A total of 4029 DCM differentially expressed genes were obtained, including 1855 upregulated genes and 2174 downregulated genes. GO/KEGG/GSEA analysis suggested that the activation of T cells and B cells was the primary cause of DCM. WGCNA was used to obtain blue module genes. The blue module genes are primarily ADCY7, BANK1, CD1E, CD19, CD38, CD300LF, CLEC4E, FLT3, GPR18, HCAR3, IRF4, LAMP3, MRC1, SYK, and TLR8, which successfully divided DCM into three molecular subtypes. Based on the CIBERSORT algorithm, the immune infiltration profile of DCM was analyzed. Many immune cell subtypes, including the abovementioned immune cells, showed different levels of increased infiltration in the myocardial tissue of DCM. However, this infiltration pattern was not obviously correlated with clinical characteristics, such as age, EF, and sex. Based on network pharmacology and ClueGO, 20 active components of Astragalus membranaceus and 40 components of DMCTGS were obtained from TCMSP. Through analysis of the immune regulatory network, we found that Astragalus membranaceus effectively regulates the activation of immune cells, such as B cells and T cells, cytokine secretion, and other processes and can intervene in DCM at multiple components, targets, and levels. The above mechanisms were verified by molecular docking results, which confirmed that AKT1, VEGFA, MMP9, and RELA are promising potential targets of DCM.

Toxicologic effect and transcriptome analysis for short-term orally dosed enrofloxacin combined with two veterinary antimicrobials on rat liver.

Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg·BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.

Array-Based Discriminative Optical Biosensors for Identifying Multiple Proteins in Aqueous Solution and Biofluids.

Identification of proteins is an important issue both in medical research and in clinical practice as a large number of proteins are closely related to various diseases. Optical sensor arrays with recognition ability have been flourished to apply for distinguishing multiple chemically or structurally similar analytes and analyzing unknown or mixed samples. This review gives an overview of the recent development of array-based discriminative optical biosensors for recognizing proteins and their applications in real samples. Based on the number of sensor elements and the complexity of constructing array-based discriminative systems, these biosensors can be divided into three categories, which include multi-element-based sensor arrays, environment-sensitive sensor arrays and multi-wavelength-based single sensing systems. For each strategy, the construction of sensing platform and detection mechanism are particularly introduced. Meanwhile, the differences and connections between different strategies were discussed. An understanding of these aspects may help to facilitate the development of novel discriminative biosensors and expand their application prospects.

Comparative Study of Pulsed Versus Continuous High-Intensity Focused Ultrasound Ablation Using In Vitro and In Vivo Models.

OBJECTIVES: To compare the efficacy of pulsed high-intensity focused ultrasound (PHIFU) versus continuous high-intensity focused ultrasound (CHIFU) ablation at identical doses. METHODS: Continuous and pulsed HIFU (1200 J) at duty cycles (DCs) of 60% and 20% were examined for their capacity to ablate bovine liver tissue in vitro and rabbit liver tissue in vivo. After ablation, grayscale changes and pathologic characteristics were observed or measured, and the tissue necrosis volume, energy efficiency factor, and average grayscale density were calculated. RESULTS: The pulsed mode generated greater liquefaction necrosis. An inconspicuous grayscale change was observed for PHIFU at a DC of 20% in some samples, which appeared as an elliptical cavity. The energy efficiency factor of PHIFU at a DC of 60% was significantly lower than that of CHIFU, as observed both in vitro and in vivo (P < .05). The grayscale value and average grayscale density in response to CHIFU were significantly greater than those in response to PHIFU (60% or 20%; P < .05). Histopathologic analysis revealed liquefaction necrosis in all PHIFU groups. CONCLUSIONS: At identical doses, compared with CHIFU, a single session of PHIFU can generate liquefaction necrosis and at a higher DC can improve ablation efficiency. This increased efficacy of PHIFU may involve enhancement of tissue destruction by cavitation effects and a reduction in the obstruction effect of endogenous microbubbles through cavitation effects or a more effective diffusion of heat.

Concise Synthesis of Open-Cage Fullerenes for Oxygen Delivery.

Open-cage fullerenes with a 19-membered orifice were prepared in three steps from C60 . The key step for cage-opening is aniline mediated ring expansion of a fullerene-mixed peroxide with a ketolactone moiety on the orifice. Release of ring strain on the spherical fullerene cage served as the main driving force for the efficient cage-opening sequence. Encapsulation of oxygen could be achieved at room temperature under moderate pressure (50 atm) and the encapsulated oxygen could be released slowly under ambient conditions. The activation energy of the oxygen-releasing process is 18.8 kcal mol-1 and the half-life at 37 °C was 73 min, which makes this open-cage fullerene derivative a potential oxygen-delivery material.

Crystal structure of (E,E)-2',4'-di-hydroxy-aceto-phenone azine di-methyl-formamide disolvate.

In the title compound {systematic name: 4,4'-[1,1'-(hydrazinediyl-idene)bis-(ethan-1-yl-1-yl-idene)]bis-(benzene-1,3-diol)}, C16H16N2O4·2C3H7NO, the (E,E)-2',4'-di-hydroxy-aceto-phenone azine mol-ecule is centrosymmetric, the mid-point of the N-N bond being located on an inversion centre. All the non-H atoms of the azine mol-ecule are approximately coplanar, the maximum deviation being 0.017 (2) Å. An intra-molecular O-H⋯N hydrogen bond occurs between the azine N atom and the hy-droxy group. In the crystal, azine and di-methyl-formamide solvent mol-ecules are linked by O-H⋯O hydrogen bonds.

Crystal structure of 1,2-bis-(2,6-di-methyl-phen-yl)-3-phenyl-guanidine.

In the title compound, C23H25N3, the dihedral angles between the planes of the benzene ring and the two substituent di-methyl-phenyl rings are 60.94 (7)° and 88.08 (7)°, and the dihedral angle between the planes of the two di-methyl-phenyl rings is 58.01 (7)°. In the crystal, weak C-H⋯N inter-actions exist between adjacent mol-ecules. One of the di-methyl-phenyl rings has a small amount of π-π overlap with the phenyl ring of an adjacent mol-ecule [centroid-to-centroid distance = 3.9631 (12) Å].

N-(2-Methyl-phen-yl)-1,2-benzoselen-azol-3(2H)-one.

IN THE TITLE EBSELEN [SYSTEMATIC NAME: (2-phenyl-1,2-benzoisoselenazol-3-(2H)-one)] analogue, C14H11NOSe, the benzisoselenazolyl moiety (r.m.s. deviation = 0.0209 Å) is nearly perpendicular to the N-arenyl ring, making a dihedral angle of 78.15 (11)°. In the crystal, mol-ecules are linked by C-H⋯O and Se⋯O inter-actions into chains along the c-axis direction. The Se⋯O distance [2.733 (3) Å] is longer than that in Ebselen (2.571 (3) Å].

A monoclinic polymorph with Z = 4 of (E)-2,4-dihy-droxy-acetophenone 2,4-dinitro-phenyl-hydrazone N,N-dimethyl-formamide monosolvate.

The title compound, C(14)H(12)N(4)O(6)·C(3)H(7)NO, is a monoclinic polymorph of an already published structure [Baughman et al. (2004 ▶). Acta Cryst. C60, 103-106]. In the previously reported structure, the compound crystallized in the triclinic space group P[Formula: see text] (Z = 2), whereas the structure reported here is monoclinic (P2(1)/n, Z = 4). In both forms, two intra-molecular hydrogen bonds result in the formation of a fairly planar hydrazone skeleton (r.m.s. deviations for all non-H atoms = 0.127 Šfor the monoclinic from and 0.131 Šfor the triclinic form) and each mol-ecule is hydrogen bonded to one solvent mol-ecule. The principal difference between the two forms lies in the different orientation of the two mol-ecules. In the monoclinic form, the two mol-ecules are almost coplanar [dihedral angle = 3.27 (2)°], whereas in the triclinic form the two mol-ecules are almost mutulally perpendicular (dihedral angle = 85.3°).

N,N'-Bis(2,3-dimeth-oxy-benzyl-idene)ethane-1,2-diamine.

The title compound, C(20)H(24)N(2)O(4), crystallizes with two half (centrosymmetric) mol-ecules in the asymmetric unit. There are only minor differences between the geometric parameters between these two mol-ecules. The two aromatic rings in both mol-ecules are mutually coplanar.

N,N'-Bis(4-methyl-benzyl-idene)benzene-1,4-diamine.

The centrosymmetric title compound, C(22)H(20)N(2), crystallizes with one half-mol-ecule in the asymmetric unit. The dihedral angle between the central and outer benzene rings is 46.2 (2)°.

Bis[µ(2)-1,1-(butane-1,4-di-yl)-2,3-dicyclo-hexyl-guanidinato]bis-[(tetra-hydro-furan)-lithium](Li-Li).

In the dinuclear centrosymmetric title complex, [Li(2)(C(17)H(30)N(3))(2)(C(4)H(8)O)(2)], the Li(+) cation is coordinated by three N atoms from two guanidinate ligands and an O atom from tetra-hydro-furan (THF) in a strongly distorted tetrahedral environment. In the guanidinate-bridged THF-stabilized dimer the Li⋯Li separation is short at 2.479 (8) Å.

[1,1-(Butane-1,4-diyl)-2,3-dicyclohexylguanidinato]dimethylaluminum(III).

In the crystal structure of the title complex, [Al(CH(3))(2)(C(17)H(30)N(3))], the Al(III) cation is coordinated by two methyl ligands and two N atoms from the guanidinato ligand in a distorted tetra-hedral geometry. The dihedral angle between the CN(2) and AlC(2) planes is 85.37 (2)°. The two N atoms of the guanidinato ligand exhibit an almost uniform affinity to the metal atom.