Sodium-dependent glucose transporter 2 inhibitor alleviates renal lipid deposition and improves renal oxygenation levels in newly diagnosed type 2 diabetes mellitus patients: a randomized controlled trial.

BACKGROUND: Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) has the advantages of effectively lowering blood glucose levels and improving renal outcomes in diabetic patients. This study evaluated the effect of canagliflozin on intrarenal lipid content and oxygenation in newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 64 newly diagnosed T2DM patients with normal renal function were randomly divided into canagliflozin (n = 33) and glimepiride control (n = 31) groups. All patients underwent functional magnetic resonance imaging (fMRI) scanning to assay patients' intrarenal lipid content and oxygenation level before and after 24 weeks of treatment. Furthermore, the relationship between body mass index and intrarenal lipid content in T2DM patients was analyzed and the correlation between changes in intrarenal lipid content and improvements in renal hypoxia was further assessed. RESULTS: The canagliflozin group had a greater decrease in body weight and blood uric acid level than the glimepiride group (all P < 0.05). The intrarenal lipid content could be significantly reduced after canagliflozin treatment for 24 weeks. The R2* values, a parameter for quantifying the oxygen content in tissues and is inversely related to the oxygen content, of the renal cortex and medulla in the canagliflozin group decreased from the baseline by 6.40% (P < 0.01) and 12.09% (P = 0.000007), respectively. In addition, the degree of reduction of fat fraction (ΔFF) in the kidneys of the canagliflozin group was correlated with the degree of improvement of oxygenation level (ΔR2*) in the renal cortex (r = 0.422, P = 0.014). CONCLUSIONS: The early renal protective effect of SGLT2i in newly diagnosed T2DM patients may be partly attributed to the amelioration of renal hypoxia via the alleviation of ectopic lipid deposition in the kidneys. TRIAL REGISTRATION: Chu Hsien-I Memorial Hospital of Tianjin Medical University (ChiCTR2000037951).

A microfluidic platform integrating dynamic cell culture and dielectrophoretic manipulation for in situ assessment of endothelial cell mechanics.

The function of vascular endothelial cells (ECs) within the complex vascular microenvironment is typically modulated by biochemical cues, cell-cell interactions, and fluid shear stress. These regulatory factors play a crucial role in determining cell mechanical properties, such as elastic and shear moduli, which are important parameters for assessing cell status. However, most studies on the measurement of cell mechanical properties have been conducted in vitro, which is labor-intensive and time-consuming. Notably, many physiological factors are lacking in Petri dish culture compared with in vivo conditions, leading to inaccurate results and poor clinical relevance. Herein, we developed a multi-layer microfluidic chip that integrates dynamic cell culture, manipulation and dielectrophoretic in situ measurement of mechanical properties. Furthermore, we numerically and experimentally simulated the vascular microenvironment to investigate the effects of flow rate and tumor necrosis factor-alpha (TNF-α) on the Young's modulus of human umbilical vein endothelial cells (HUVECs). Results showed that greater fluid shear stress results in increased Young's modulus of HUVECs, suggesting the importance of hemodynamics in modulating the biomechanics of ECs. In contrast, TNF-α, an inflammation inducer, dramatically decreased HUVEC stiffness, demonstrating an adverse impact on the vascular endothelium. Blebbistatin, a cytoskeleton disruptor, significantly reduced the Young's modulus of HUVECs. In summary, the proposed vascular-mimetic dynamic culture and monitoring approach enables the physiological development of ECs in organ-on-a-chip microsystems for accurately and efficiently studying hemodynamics and pharmacological mechanisms underlying cardiovascular diseases.

Tissue perfusion of the kurtosis/diffusion mismatch differs from the central core and peripheral regions in acute cerebral infarction patients.

BACKGROUND: Despite its wide adoption in stroke imaging, the diffusion-weighted imaging (DWI) lesion is heterogeneous. The emerging diffusion kurtosis imaging (DKI) has been postulated to resolve the graded DWI lesion. PURPOSE: To determine the perfusion characteristics of the central infarction core, kurtosis/diffusion mismatch, and peripheral regions. MATERIAL AND METHODS: Patients with acute ischemic stroke underwent DWI, DKI, and perfusion-weighted imaging (PWI) scans. The patients were divided into mean kurtosis (MK)/mean diffusivity (MD) match and mismatch groups. Perfusion parameters were measured in the MK/MD lesion and peripheral areas in the MK/MD match group. We also analyzed perfusion status in the MK/MD lesion mismatch area for the mismatch group. RESULTS: A total of 40 eligible patients (24 MK/MD match and 16 MK/MD mismatch) were enrolled in the final data analysis. The MTT and TTP progressively decreased, while the cerebral blood flow (CBF) and cerebral blood volume (CBV) increased from the central to peripheral areas. In addition, CBF in the MK/MD mismatch region was significantly higher than that in the central region (P < 0.05), but similar to the peripheral region. Furthermore, CBV in the MK/MD mismatch region did not differ significantly from that of the central region, but both were significantly lower than that of the peripheral area (P < 0.05). CONCLUSION: The MK/MD mismatch region had blood flow similar to the peripheral region but with a reduced blood volume, indicating that it was less ischemic from the infarction core, albeit insufficient collateral circulation.

Analysis of Sequential Micromixing Driven by Sinusoidally Shaped Induced-Charge Electroosmotic Flow.

Multi-fluid micromixing, which has rarely been explored, typically represents a highly sought-after technique in on-chip biochemical and biomedical assays. Herein, we propose a novel micromixing approach utilizing induced-charge electroosmosis (ICEO) to implement multicomplex mixing between parallel streams. The variations of ICEO microvortices above a sinusoidally shaped floating electrode (SSFE) are first investigated to better understand the microvortex development and the resultant mixing process within a confined channel. On this basis, a mathematical model of the vortex index is newly developed to predict the mixing degree along the microchannel. The negative exponential distribution obtained between the vortex index and mixing index demonstrates an efficient model to describe the mixing performance without solving the coupled diffusion and momentum equations. Specifically, sufficient mixing with a mixing index higher than 0.9 can be achieved when the vortex index exceeds 51, and the mixing efficiency reaches a plateau at an AC frequency close to 100 Hz. Further, a rectangle floating electrode (RFE) is deposited before SSFE to enhance the controlled sequence for three-fluid mixing. One side fluid can fully mix with the middle fluid with a mixing index of 0.623 above RFE in the first mixing stage and achieve entire-channel mixing with a mixing index of 0.983 above SSFE in the second mixing stage, thereby enabling on-demand sequential mixing. As a proof of concept, this work can provide a robust alternative technique for multi-objective issues and structural design related to mixers.

Dielectrophoretic medium exchange around droplets for on-chip fabrication of layer-by-layer microcapsules.

Continuous medium exchange within a microchannel represents a highly sought-after technique in functionalizing micro-objects with coating layers, enabling a myriad of applications ranging from biomedical engineering to materials science. Herein, we introduce a unique medium exchange approach, namely, tilted-angle dielectrophoresis, to accomplish layer-by-layer (LbL) coating on droplets in a wide microchannel. Pairs of adjacent tilted parallel electrodes arranged in a zigzag fashion are exploited to consecutively and repeatedly guide particles/droplets travelling through three parallel laminar streams comprising two reagents and a washing buffer. The performance of medium exchange is demonstrated using PS microparticles and oil droplets. We show that multi-cycle medium exchange, droplet transfer accompanied with purification, and multi-mode medium exchange around different micro-objects are achieved by conveniently regulating the applied voltage and the inlet flow rate, indicating a flexible, versatile and label-free alternative for characterizing and handling colloidal particles. Furthermore, LbL coating on droplets utilizing the presented strategy is implemented in the parallel coating-chemical and washing streams to obtain multiple layers of microcapsules. The linearly increasing fluorescence intensity of the coated droplets with each subsequent fluorescent coating demonstrates the capability of the tilted-angle dielectrophoretic medium exchanger for on-chip generation of LbL microcapsules on demand. The presented medium exchange strategy, together with its unique features of simple geometric configuration, facile control and multifunctionality, can provide a refined alternative for further expanding the utility scope in functional particles and cells.

Flexible online in-droplet cell/synthetic particle concentration utilizing alternating current electrothermal-flow field-effect transistor.

Cell/particle concentration inside droplets holds great potential in extending lab-in-a-droplet applications, typically ranging from biological and chemical assays. Herein, we present a universal, massive and versatile technique, namely, alternating current electrothermal-flow field-effect transistor (ACET-FFET) to accomplish in-droplet cell/synthetic particle concentration on demand. Three parallel planar electrodes are utilized to generate an artificially reorderable electric field inside droplets by tuning the gate voltage through field-effect control, which results in a reshapable ACET-based microvortices pattern for in-droplet concentration. A downstream Y-shaped junction promotes the mother droplet splitting into two daughter droplets containing highly and poorly concentrated cells/particles, respectively. Fluorescent polystyrene (PS) nanoparticles are used to characterize the variations of ACET-microvortices flow pattern formation within droplets. Moreover, the concentration performance is demonstrated using PS microparticles and Neurospora crassa cells. We show that particles/cells can flexibly accumulate into any daughter droplet or be equally concentrated in both daughter droplets by conveniently regulating the gate voltage. The highly concentrated cells at the entrance of the concentrator show an instantaneous response performance to the external electric field. Further, online simultaneous particle synthesis and concentration inside droplets are proposed and implemented for the first time, demonstrated by efficient in-droplet micromixing and Prussian blue (PB) reaction. The accompanying synthetic PB particles are highly concentrated into either daughter droplet, thereby extending the versatility of the platform. The presented in-droplet concentration strategy, together with its unique features of simple geometric configuration, facile operation and broad applicability can broaden utility in droplet microfluidics.

Dielectrophoresis Response of Water-in-Oil-in-Water Double Emulsion Droplets with Singular or Dual Cores.

Microfluidic technologies have enabled generation of exquisite multiple emulsion droplets, which have been used in many fields, including single-cell assays, micro-sized chemical reactions, and material syntheses. Electrical controlling is an important technique for droplet manipulation in microfluidic systems, but the dielectrophoretic behaviors of multiple emulsion droplets in electrical fields are rarely studied. Here, we report on the dielectrophoresis response of double emulsion droplets in AC electric fields in microfluidic channel. A core-shell model is utilized for analyzing the polarization of droplet interfaces and the overall dielectrophoresis (DEP) force. The water-in-oil-in-water droplets, generated by glass capillary devices, experience negative DEP at low field frequency. At high frequency, however, the polarity of DEP is tunable by adjusting droplet shell thickness or core conductivity. Then, the behavior of droplets with two inner cores is investigated, where the droplets undergo rotation before being repelled or attracted by the strong field area. This work should benefit a wide range of applications that require manipulation of double emulsion droplets by electric fields.

Continuous Particle Trapping, Switching, and Sorting Utilizing a Combination of Dielectrophoresis and Alternating Current Electrothermal Flow.

We propose a simplified multifunctional traffic control approach that effectively combines dielectrophoresis (DEP) and alternating current electrothermal (ACET) flow to realize continuous particle trapping, switching, and sorting. In the designed microsystem, the combined DEP and ACET effects, which are symmetrically generated above a bipolar electrode surface, contribute to focus the incoming colloidal particles into a thin beam. Once the bipolar electrode is energized with an electric gate signal completely in phase with the driving alternating current (AC) signal, the spatial symmetry of the electric field can be artificially reordered by adjusting the gate voltage through field-effect traffic control. This results in a reshapable field stagnant region for precise switching of particles into the region of interest. Moreover, the integrated particle switching prior to the scaled particle trapping experiment is successfully conducted to demonstrate the feasibility of the combined strategy. Furthermore, a mixture of two types of particle sorting (i.e., density, size) with quick response performance is achieved by increasing the driving voltage with a maximum gate voltage offset, thus, extending the versatility of the designed device. Finally, droplet switching and filtration of the satellite droplets from the parent droplets is performed to successfully permit control of the droplet traffic. The proposed traffic control approach provides a promising technique for flexible manipulation of particulate samples and can be conveniently integrated with other micro/nanofluidic components into a complete functional on-chip platform owing to its simple geometric structure, easy operation, and multifunctionality.

Flexible Continuous Particle Beam Switching via External-Field-Reconfigurable Asymmetric Induced-Charge Electroosmosis.

Continuous sample switching is an essential process for developing an integrated platform incorporating multiple functionality with applications typically ranging from chemical to biological assays. Herein we propose a unique method of external-field-reconfigurable symmetry breaking in induced-charge electroosmosis above a simple planar bipolar electrode for continuous particle beam switching. In the proposed system, the spatial symmetry of a nonlinear electroosmotic vortex flow can be artificially reordered to achieve an asymmetric electrically floating-electrode polarization by regulating the configurations of the external ac signals, thus contributing to flexible particle beam switching. This switching system comprises an upstream flow-focusing region where particles are prefocused into a beam on the bipolar electrode by transversal electroconvective mass transfer, and a deflecting region in which the resulting particle beam is deflected to generate a steerable lateral displacement to enter the desired region via the action of an asymmetric polarization-induced reshapable electroosmotic flow stagnation line in a controllable background field gradient. A lateral particle displacement on the order of hundreds of micrometers can be achieved in a deterministic manner by varying the voltage, frequency, and inlet flow rate, thereby enabling multichannel particle switching. Furthermore, the versatility of the switching mechanism is extended by successfully accomplishing fluorescent nanoparticle beam switching, yeast cell switching, five-outlet particle switching, and simultaneous switching of two particle types. The proposed switching approach provides a promising technique for flexible electrokinetic sample preconcentration prior to any subsequent analysis and can be conveniently integrated with other micro/nanofluidic components into a complete functional on-chip platform owing to its simple electrode structure.

Diffusion Kurtosis Imaging of Acute Infarction: Comparison with Routine Diffusion and Follow-up MR Imaging.

Purpose To determine the relationship between diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in patients with acute stroke at admission and the tissue outcome 1 month after onset of stroke. Materials and Methods Patients with stroke underwent DWI (b values = 0, 1000 sec/mm2 along three directions) and DKI (b values = 0, 1000, 2000 sec/mm2 along 20 directions) within 24 hours after symptom onset and 1 month after symptom onset. For large lesions (diameter ≥ 1 cm), acute lesion volumes at DWI and DKI were compared with those at follow-up T2-weighted imaging by using Spearman correlation analysis. For small lesions (diameter < 1 cm), the number of acute lesions at DWI and DKI and follow-up T2-weighted imaging was counted and compared by using the McNemar test. Results Thirty-seven patients (mean age, 58 years; range, 35-82 years) were included. There were 32 large lesions and 138 small lesions. For large lesions, the volumes of acute lesions on kurtosis maps showed no difference from those on 1-month follow-up T2-weighted images (P = .532), with a higher correlation coefficient than those on the apparent diffusion coefficient and mean diffusivity maps (R2 = 0.730 vs 0.479 and 0.429). For small lesions, the number of acute lesions on DKI, but not on DWI, images was consistent with that on the follow-up T2-weighted images (P = .125). Conclusion DKI complements DWI for improved prediction of outcome of acute ischemic stroke. © RSNA, 2018.

Pyrolysis of chitin biomass: TG-MS analysis and solid char residue characterization.

The thermal degradation of chitin biomass with various molecular structures was investigated by thermogravimetric analysis (TG), and the gaseous products were analyzed by connected mass spectroscopy (MS). The chemical structure and morphology of char residues collected at 750°C using the model substrates GlcNH2 and GlcNAc, were characterized systematically. The experimental results disclosed that one main mass loss stage was observed for each substrate. Chitosan samples with high molecular weight shown the more thermal stability, and chitin showed the highest thermal stability. Additionally, it was found that catalysts play a significant role during the pyrolysis. The gaseous evolution components, including NH3, H2O, CO, and CO2 were observed by on line MS. The experimental results disclosed that the obtained carbonaceous materials had lost the original hydrocarbon structure totally, and transformed into an aromatic structure with high carbon and nitrogen content, which was identified by XPS and solid state NMR.

Hollow Porous Carbon Fiber from Cotton with Nitrogen Doping.

Porous carbon fiber with hollow structure and hydrophilic groups was successfully prepared from cotton. The structures and surface chemical properties of the porous carbon fiber were characterized by nitrogen adsorption isotherms, thermogravimetry, FTIR spectroscopy, and scanning electron microscopy. The morphologies of porous carbons prepared under different conditions were observed and compared. The resulting porous carbons had a microporous structure with a pore size distribution around 0.7-2.0 nm. The pyrolysis and decomposition of cotton to form a condensation cross-linked ring structure took place from 230 to 350 °C. Nitrogen-containing groups could be incorporated into the carbon matrix by urea decomposition during the carbonization process. The porous carbon contained more hydrophilic groups and its fiber structure was kept; the carbon yield was improved in the presence of KOH/urea. The porous carbon fiber showed high adsorption capacities of CO2 as a result of its surface hydrophilic groups and developed pore structure.

Preparation, characterization and photocatalytic properties of CdS nanoparticles dotted on the surface of carbon nanotubes.

Cadmium sulfide (CdS) nanoparticles dotted on the surface of multiwalled carbon nanotubes (MWCNTs) have been synthesized by the polyol method. The as-prepared materials were characterized by x-ray powder diffraction, transmission electron microscopy, scanning electron microscopy, and Brunauer-Emmett-Teller adsorption analysis. The results indicate that CdS nanoparticles with diameter of 5-8 nm are thickly and uniformly coated on the surface of the MWCNTs. The photodegradation of azo dye using these materials was evaluated by the degradation of Brilliant Red X-3B under visible light. The coated nanotubes show higher photocatalytic activity than both CdS alone and a CdS/activated carbon sample; in addition, there is an optimum content of MWCNTs. The presence of MWCNTs can also hamper the photocorrosion of CdS. The mechanism for the enhancement of MWCNTs on the adsorption and photocatalytic property of CdS is investigated for the first time.