An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening.

Background: Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions.

Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition.

A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2).

Visualizing an ultra-weak protein-protein interaction in phosphorylation signaling.

Proteins interact with each other to fulfill their functions. The importance of weak protein-protein interactions has been increasingly recognized. However, owing to technical difficulties, ultra-weak interactions remain to be characterized.

Probing dynamics and mechanism of exchange process of quaternary ammonium dimeric surfactants, 14-s-14, in the presence of conventional surfactants.

In this Article, we investigated effects of different types of conventional surfactants on exchange dynamics of quaternary ammonium dimeric surfactants, with chemical formula C(14)H(29)N(+)(CH(3))(2)- (CH(2))(s)-N(+)(CH(3))(2)C(14)H(29)·2Br(-), or 14-s-14 for short. Two nonionic surfactants, TritonX-100 (TX-100) and polyethylene glycol (23) laurylether (Brij-35), and one cationic surfactant, n-tetradecyltrimethyl ammonium bromide (TTAB), and one ionic surfactant, sodium dodecyl sulfate (SDS) were chosen as typical conventional surfactants. Exchange rates of 14-s-14 (s = 2, 3, and 4) between the micelle form and monomer in solution were detected by two NMR methods: one-dimensional (1D) line shape analysis and two-dimensional (2D) exchange spectroscopy (EXSY).

Structural and functional diversity of acidic scorpion potassium channel toxins.

Background: Although the basic scorpion K(+) channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K(+) channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly.

Principal Findings: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses.

NMR study of the dynamics of cationic gemini surfactant 14-2-14 in mixed solutions with conventional surfactants.

Three kinds of conventional surfactants, namely, two nonionic surfactants [polyethylene glycol (23) lauryl ether (Brij-35) and Triton X-100 (TX-100)], one cationic surfactant [n-tetradecyltrimethyl ammonium bromide (TTAB)], and an anionic surfactant [sodium n-dodecyl sulfate (SDS)}, were mixed into the quaternary ammonium gemini surfactant [C(14)H(29)N(+)(CH(3))(2)](2)(CH(2))(2).2Br(-) (14-2-14) in aqueous solution. The exchange rate constants between 14-2-14 molecules in the mixed micelles and those in the bulk solution were detected using two nuclear magnetic resonance (NMR) methods: one-dimensional (1D) line shape analysis and two-dimensional (2D) exchange spectroscopy (EXSY).

Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels.

The low selectivity of Kv1 peptide inhibitors for specific isoforms makes them poor candidates for the development of theraputics. Using combined approaches, we showed that the Kv1 turret is the critical determinant for ADWX-1 peptide inhibitor selectivity of Kv1.3 over Kv1.

1H NMR study on pre-micellization of quaternary ammonium gemini surfactants.

Two quaternary ammonium Gemini surfactant series, 12-s-12, ([C(12)H(25)N+ (CH(3))(2)](2)(CH(2))(s).(2)Br(-)) and 14-s-14 ([C(14)H(29)N(+)(CH(3))(2)](2)(CH(2))(s).(2)Br(-)), where s = 2, 3, and 4, have been studied by the use of (1)H NMR in aqueous solution at concentrations below their critical micelle concentrations (CMC) at 25 degrees C.

Polyaspartamide gadolinium complexes containing sulfadiazine groups as potential macromolecular MRI contrast agents.

Both diethylenetriaminepentaacetic acid (DTPA) and sulfadiazine (SD) were incorporated into polyaspartamides with different side chains, including poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA), poly-alpha,beta-[N- (3-hydroxypropyl)-L-aspartamide] (PHPA), poly-alpha,beta-[N-(2-aminoethy1)-L-aspartamide] (PAEA), poly-alpha,beta-[N-(4-aminobuty1)-L-aspartamide] (PABA), and poly-alpha,beta-[N-(6-aminohexyl)-L-aspartamide] (PAHA). The polyaspartamide ligands containing DTPA and SD groups were further reacted with gadolinium chloride to give the corresponding macromolecular gadolinium complexes. Experimental data of 1H NMR, IR, UV, and elemental analysis exhibited the formation of the polyaspartamide ligands and gadolinium complexes.

Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents.

Diethylenetriaminepentaacetic acid (DTPA) and pyridoxamine (PM) were incorporated into the amine groups on the surface of ammonia-core poly(amidoamine) dendrimers (PAMAM, Generation 2.0-5.0) to obtain dendritic ligands.

Correlation of behavior changes and BOLD signal in Alzheimer-like rat model.

To explore a potential means for the early diagnosis of Alzheimer disease, we studied the relationship of resting T2* signal and tau hyperphosphorylation/spatial memory deficit. The rat model with tau hyperphosphorylation and spatial memory deficit was established by bilateral hippocampi injection of isoproterenol (IP). Then, the correlative alteration between resting T2* signal and spatial memory retention was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) study and Morris Water Maze test, and Western blot was employed to confirm tau hyperphosphorylation.

[The effects of Erigeron breviscapus preparation on the imaging and neuronal metabolites at the early time points after reperfusion following the ischemic cerebral injury in rats].

Objective: To investigate the effects of Erigeron breviscapus preparation on the imaging and neuronal metabolites after reperfusion in the ischemic cerebral injury in rats.

Method: Twenty-three male Sprague Dawley rats with an average body weight of (165 +/- 15) g (mean +/- S) were used, and were randomly divided into two groups: group A rats (n = 11) underwent an operation of ischemic brain injury, group B rats (n = 12) underwent the same operation and received the treatment of Erigeron breviscapus preparation (1.5 mg.

[Effects of Angelica sinensis injection on the neuronal metabolites and blood flow speed within reperfusion following the ischemic cerebral injury in rats].

Aim: To investigate the effects of Angelica sinensis injection on the neuronal metabolites and blood flow speed within reperfusion in the ischemic cerebral injury of rats.

Methods: Sixty-nine male Sprague Dawley rats with an average body weight of 150 to 170 g were used, and were randomly divided into three groups: sham operation group (n = 4), ischemia injury group (n = 30) underwent an operation of ischemic brain injury, Angelica-treated group (n = 35) underwent the same operation and received the treatment of Angelica sinensis injection (5 g/kg bw, i. p).

[Propagation of brain injuries from artificial focus into the opposite hemisphere at the early stage of rat electrogenic epilepsy identified by histology and magnetic resonance image].

The purpose of this work was to study the characteristics of rat brain abnormalities at two hemispheres at the early stage of electrogenic epilepsy. Experiments were performed on 37 male Sprague-Dawley rats. Chronically repetitive tetanization (60 Hz, 2 s, 0.

A study on human urine in a high-selenium area of China by 1H-NMR spectroscopy.

In this study, high-resolution 600-MHz 1H-NMR (nuclear magnetic resonance) spectroscopies were used to compare the urinary metabolic profiles of healthy humans and humans in a high-selenium area of China. NMR biomarkers for renal and liver lesions were observed by comparing the urine 1H-NMR spectra. In urinary excretion, the concentrations in human urine samples of formate, lactate, acetate, hippurate, and alanine in overexposure to selenium were increased, whereas citrate, creatine, and TMAO excretion were decreased compared with that of the healthy human--some of them even disappeared.

Detection of an unkown peak at 1.2 ppm in proton magnetic resonance spectra of cats with cerebral ischemic necrosis.

Objective: To confirm an unknown peak (Pu) in proton magnetic resonance spectra ((1)H-MRS) in cats with permanent focal cerebral ischemia, and surmise its potential value of application.

Methods: After focal cerebral ischemia, diffusion-weighted imaging (DWI) was used to identify regions of ischemia for (1)H-MRS voxel localization with the assistance of stereotaxic atlas of cat brain. (1)H-MRS was used to monitor the progression of focal cerebral ischemia in 6 cats over a period of 7 d following middle cerebral artery occlusion (MCAO).

NMR study on the low-affinity interaction of human serum albumin with diclofenac sodium.

The low-affinity interaction between human serum albumin (HSA) and Diclofenac sodium (DCF) was studied using NMR techniques. Both 13C-NMR chemical shift and linewidth show that the dichlorophenyl ring in DCF molecule plays a primary role in its interaction with HSA. Langmuir adsorption isotherm was applied to evaluate the association constant K and the number of binding sites n of the drug/HSA complex through (1)H-NMR spin-lattice relaxation measurement.

[Development and progression in rat brain abnormalities related to early stage of epilepsy measured by magnetic resonance image].

The purpose of the present study was to investigate the features of pathophysiological neural networks in rat temporal lobe epileptogenesis. To establish electrogenic epilepsy model, repetitive tetanization (60 Hz, 2 s, 0.4-0.