Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases.

The endoplasmic reticulum, a key cellular organelle, regulates a wide variety of cellular activities. Endoplasmic reticulum autophagy, one of the quality control systems of the endoplasmic reticulum, plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover, remodeling, and proteostasis. In this review, we briefly describe the endoplasmic reticulum quality control system, and subsequently focus on the role of endoplasmic reticulum autophagy, emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements. We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases. In summary, this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders. This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

Effects of different helmet-mounted devices on pilot's neck injury under simulated ejection.

The helmet plays an important role in protection of pilot's head and enhances the pilot's capabilities and performance significantly with the use of mounted devices such as the Night Vision Goggle (NVG). However, the use of helmet-mounted devices might increase the risk of injury due to the increased helmet weight and change in the centre of gravity of head. In this study, four helmets with different combinations of mounted devices were modelled in a validated human head-neck multi-body model to analyse their effects on the pilot's neck injury during simulated ejection. The probability of neck injury was evaluated and predicted using the Nij neck injury criteria and human injury risk curves, considering the tolerance of injury for upper and lower cervical segment. It was demonstrated that the helmet-mounted devices would increase the compression force and bending moment on cervical spine, especially for the lower cervical segments with higher Nij. In the cases with Night Vision Goggle, Nij of the lower cervical segment reached 0.54, which exceeded the requirement in aviation filed. For the cases with Visor, excessive extension occurred, resulting in a high Nij. The simulation results of this study could provide a reference for helmet and mounted devices design and offer a proposal for the protection of pilots during ejection.

TRIM32 Deficiency Impairs the Generation of Pyramidal Neurons in Developing Cerebral Cortex.

Excitatory-inhibitory imbalance (E/I) is a fundamental mechanism underlying autism spectrum disorders (ASD). TRIM32 is a risk gene genetically associated with ASD. The absence of TRIM32 causes impaired generation of inhibitory GABAergic interneurons, neural network hyperexcitability, and autism-like behavior in mice, emphasizing the role of TRIM32 in maintaining E/I balance, but despite the description of TRIM32 in regulating proliferation and differentiation of cultured mouse neural progenitor cells (NPCs), the role of TRIM32 in cerebral cortical development, particularly in the production of excitatory pyramidal neurons, remains unknown. The present study observed that TRIM32 deficiency resulted in decreased numbers of distinct layer-specific cortical neurons and decreased radial glial cell (RGC) and intermediate progenitor cell (IPC) pool size. We further demonstrated that TRIM32 deficiency impairs self-renewal of RGCs and IPCs as indicated by decreased proliferation and mitosis. A TRIM32 deficiency also affects or influences the formation of cortical neurons. As a result, TRIM32-deficient mice showed smaller brain size. At the molecular level, RNAseq analysis indicated reduced Notch signalling in TRIM32-deficient mice. Therefore, the present study indicates a role for TRIM32 in pyramidal neuron generation. Impaired generation of excitatory pyramidal neurons may explain the hyperexcitability observed in TRIM32-deficient mice.

Integrated Digital Microfluidic Platform for Colorimetric Sensing of Nitrite.

In this paper, a palm-size digital microfluidic (DMF) platform integrated with colorimetric analysis was developed for quantifying the concentration of nitrite. To realize the on-chip repeatable colorimetric analysis, a novel printed circuit board (PCB)-based DMF chip was designed with an embedded aperture on the actuator electrode, forming a vertical light path for online measurement of the droplets. The capabilities of the DMF platform enable automatic manipulation of microliter-level droplets to implement Griess assay without the use of external systems such as syringe, pump, or valve, which provides the benefits including high flexibility, portability, miniature size, and low cost. Results indicated the characteristics of good linearity (R 2 = 0.9974), the ignorable crosstalk for reusability, and the limit of detection (LOD) of nitrite as low as 5 µg/L. Furthermore, the presented platform was successfully applied to determine nitrite levels in food products with reliable results and satisfactory recoveries. This integrated DMF platform can be a promising new tool for a wide range of applications involving step-by-step solution mixing and optical detection in environmental monitoring, food safety analysis, and point-of-care testing.

Near-Infrared Diffuse Reflectance Measurement Method Based on Temperature-Insensitive Radial Distance.

The variation of temperature is one of the main interference factors that affect the detection accuracy of near-infrared (NIR) diffuse reflectance. In this paper, a measurement method based on temperature-insensitive radial distance was proposed, and its feasibility and effectiveness were verified in Intralipid solutions. First, the possibility of temperature-insensitive radial distance was deduced based on the analytic solution of the steady-state diffusion equation in an infinite media, and the temperature-insensitive radial distances of 3% Intralipid solution in the wavelength range of 1000-1600 nm was calculated. Second, a detection system was designed to measure the diffuse reflectance of 3% Intralipid solutions at multiple radial distances with different glucose concentration (0-100 mM) and different temperatures (35-40 ℃). Both theoretical calculations and experimental results demonstrated the existence of temperature-insensitive radial distances in the range of 1000-1340 nm and 1440-1600 nm, and the distances were hardly affected by glucose variations. Finally, the glucose information extracted from the diffuse reflectance of Intralipid solutions at different radial distances under random temperature variations and constant temperature were compared. The result showed that the correlation between the glucose concentration and the diffuse reflectance obtained at the temperature-insensitive radial distance was significantly better than that of other radial distances, which was almost close to the situation of constant temperature. Therefore, the measurement method based on temperature-insensitive radial distance can effectively reduce the influence of temperature variations on NIR diffuse reflectance, and it is expected to improve the accuracy of diffuse reflectance in human body components detection and industrial field analysis.

Analysis of acrylamide in food products by microchip electrophoresis with on-line multiple-preconcentration techniques.

In this paper, a microchip electrophoresis method based on on-line multiple-preconcentration techniques combining field-amplified sample stacking and reversed-field stacking was developed for highly efficient analysis of acrylamide in food products. The related mechanism as well as important parameters governing separation and preconcentration have been investigated in order to obtain maximum resolution and sensitivity. The best separation was achieved using a 100mM borate solution at pH 9.3 as running buffer, and a sensitivity enhancement factor of 432 was obtained using this concentration method under optimal conditions. The detection limit of acrylamide was 1ng/mL, which was comparable to those previously obtained using CE methods with on-line preconcentration techniques and was 41-700 times lower than those previously reported CE methods without concentration process. The proposed method also gave satisfactory and reliable results in the analysis of acrylamide in potato chips and French fries.

Sensitive analysis of antibiotics via hyphenation of field-amplified sample stacking with reversed-field stacking in microchip micellar electrokinetic chromatography.

An on-chip multiple-concentration method combining field-amplified sample stacking (FASS) and reversed-field stacking (RFS) in microchip micellar electrokinetic chromatography (MCMEKC) was developed for the simultaneous analysis of three antibiotics (kanamycin, vancomycin, and gentamycin) using poly (styrene sulfonic acid) sodium salt (PSS) as the pseudostationary phase. Results indicated that the polymeric surfactant PSS provided high stability, unique selectivity, and high efficiency for the separation of these antibiotics as compared to SDS micelles, and the multiple-preconcentration strategy could greatly improve the sensitivity enhancement over those classical CE-LIF methods for antibiotics detection. The stacking and separation mechanism as well as important parameters governing preconcentration and separation have been investigated in order to obtain maximum resolution and sensitivity. Under optimal conditions, three antibiotics were successfully focused and completely separated within <3min. The limits of detection for kanamycin, vancomycin, and gentamycin were 0.25, 0.20, and 0.80µg/L (S/N=3), respectively, and the detection sensitivities were improved 259-, 296-, and 308-fold, respectively. The method also gave accurate and reliable results in the analysis of these antibiotics in river water samples.

Sensitive analysis of amino acids and vitamin B3 in functional drinks via field-amplified stacking with reversed-field stacking in microchip electrophoresis.

An on-line preconcentration strategy combining field-amplified stacking and reversed-field stacking was developed for efficient and sensitive analysis of amino acids and vitamin B3 including lysine (Lys), taurine (Tau), and niacinamide (NA) by microchip electrophoresis with LIF detection. In this technique, the addition of a reversed-polarity step termed reversed-field stacking could enhance the preconcentration effect of field-amplified stacking and push most of the sample matrix out of the separation channel, thus greatly improving the sensitivity enhancement by 1-2 orders of magnitude over the classical MCE-LIF methods. The related mechanism as well as important parameters governing preconcentration and separation have been investigated in order to obtain strongest sensitivity amplification and maximum resolution. Under optimal conditions, all analytes were successfully focused and completely separated within 4 min. The limits of detection for Lys, Tau, and NA were 0.25, 0.50, and 0.20 nM (S/N=3), respectively, and enhancement factors of 165-, 285-, and 236-fold were obtained for Lys, Tau, and NA as compared to using the no concentration step. Other validation parameters such as linearity and precision were considered as satisfactory. The proposed method also gave accurate and reliable results in the analysis of these functional ingredients in eight functional drink samples.

Sensitive determination of four ß2-agonists in pig feed by capillary electrophoresis using on-line sample preconcentration with contactless conductivity detection.

In this work, an on-line preconcentration method of field-enhanced sample injection (FESI) was implemented in the determination of four ß2-agoinsts terbutaline (TER), procaterol (PRO), formoterol (FOR) and bambuterol (BAM) by capillary electrophoresis coupled with capacitively coupled contactless conductivity detection (CE-C4D). Under optimized conditions the background electrolyte (BGE) was 5mM Tris(hydroxymethyl)aminomethane (Tris) and 10mM citric acid (Cit) at a pH of 3.2 while the sample dilution solution was obtained by methanol. The detection limits (defined as S/N=3) of this method were 0.02mg/L for TER, PRO, FOR, BAM, which were much lower than that of the conventional CE-C4D method without preconcentration procedure, the enhancement factors were greatly improved to be 30-40-fold. The linearity ranges of four ß2-agoinsts were 0.1-15mg/L, with good linear correlation coefficients (r2>0.9900). In order to evaluate the application potential of the developed method, real sample from pig feed was analyzed with recoveries of 91.4-106.2%.