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A novel assay platform consisting of a finger pump microchip (FPM) and a WiFi-based analytical detection platform is presented for measuring the concentration of methylparaben (MP) in commercial foods. In the presented approach, a low quantity (5 μL) of distilled food sample is dripped onto the FPM and undergoes a modified Fenton reaction at a temperature of 40 °C to form a green-colored complex. The MP concentration is then determined by measuring the color intensity (RGB) of the reaction complex using APP software (self-written) installed on a smartphone. The color intensity Red(R) + Green(G) value of the reaction complex is found to be linearly related (R

Objective: To modify the current neural tube defect (NTD) classification for fetal medicine specialists, and to investigate the impact of prenatal ultrasound conus medullaris position screening on the detection rate of closed spinal dysraphism and pregnancy outcomes. Materials and methods: The clinical data of 112 patients prenatally diagnosed with neural tube defects in Taiji clinic from 2008 to 2018 were retrospectively analyzed. All cases were classified following the modified classification. We compared the detection rate before and after introducing the conus medullaris screening and pregnancy outcomes for NTD types. Results: Closed spinal dysraphism type prevailed in our sample (43.8%). The median gestational age at the time of detection for cranial dysraphism was 13.3 weeks, open spinal dysraphism was 22.0 weeks, and closed spinal dysraphism was 22.6 weeks. All cranial dysraphism (n = 43) and open spinal dysraphism cases (n = 20) had pregnancies terminated. For closed spinal dysraphism Class 1, the live-birth rate was 100.0% in the cases without other anomalies and 33.3% in the cases with other anomalies, respectively (X2 = 17.25, p

An electrochemical-biosensor (EC-biosensor) microchip consisting of screen-printed electrodes and a double-layer reagent paper detection zone impregnated with amaranth is proposed for the rapid determination of microalbuminuria (MAU) in human urine samples. Under the action of an applied deposition potential, the amaranth is adsorbed on the electrode surface and the subsequent reaction between the modified surface and the MAU content in the urine sample prompts the formation of an inert layer on the electrode surface. The inert layer impedes the transfer of electrons and hence produces a drop in the response peak current, from which the MAU concentration can then be determined. The measurement results obtained for seven artificial urine samples with known MAU concentrations in the range of 0.1–40 mg/dL show that the measured response peak current is related to the MAU concentration with a determination coefficient of R2 = 0.991 in the low concentration range of 0.1–10 mg/dL and R2 = 0.996 in the high concentration range of 10–40 mg/dL. Furthermore, the detection results obtained for 82 actual chronic kidney disease (CKD) patients show an excellent agreement (R2 = 0.988) with the hospital analysis results. Overall, the results confirm that the proposed detection platform provides a convenient and reliable approach for performing sensitive point-of-care testing (POCT) of the MAU content in human urine samples.

Cyclamate is an artificial sweetener with high sweetness and low calories, and is a common sugar substitute for weight control and diabetic patients. However, excessive cyclamate consumption is associated with various health disorders, and hence it is prohibited as a food additive in many countries around the world. The current research proposes a light-shading reaction microfluidic PMMA/paper detection (MPD) system for determining the cyclamate concentration in food. In the current system, inject 10 μL of the extracted sodium cyclamate sample into the sample chamber of the MPD device, perform the diazotization reaction under shading conditions, and then suck it into the detection area through a paper strip, which consists of a paper chip embedded with modified Bratton-Marshall reagent. Once the paper chip is thoroughly wetted, the MPD device is inserted into a microanalysis box, where a fuchsia azo reaction compound is produced through heating at 40 °C for 3 min. The reaction complex is observed by a camera and the reaction image is wirelessly transmitted to a smartphone, and the concentration of sodium cyclamate is measured through the self-developed grayscale software. The results obtained for the sodium cyclamate samples with a concentration in the range of 50-1000 ppm show that the measured gray value changes linearly with the sodium cyclamate concentration, and the correlation coefficient (R

This study investigated whether glutamine (GLN) pretreatment can enhance circulating endothelial progenitor cells (EPCs) and attenuate inflammatory reaction in high-fat diet-induced obese mice with limb ischemia. Mice were assigned to a normal control (NC), high-fat control (HC), limb ischemia (HI), and GLN limb ischemia (HG) groups. The NC group provided chow diet and treated as a negative control. Mice in the HC and HI groups were fed a high-fat diet which 60% energy provided by fat for 8 weeks. Mice in the HG group were fed the same diet for 4 weeks and then transferred to a high-fat diet with 25% of total protein nitrogen provided as GLN to replace part of the casein for the subsequent 4 weeks. After feeding 8 weeks, mice in the HC group were sham-operated, while the HI and HG groups underwent an operation to induce limb ischemia. All mice except the NC group were euthanized on either day 1 or 7 after the operation. The results showed that the 8 weeks’ high-fat diet feeding resulted in obesity. The HG group had higher circulating EPCs on day 1 while muscle vascular endothelial growth factor, matrix metalloproteinase-9, and hypoxia-inducible factor-1 gene expressions were higher on day 7 postischemia than those of the HI group. The superoxide dismutase activity and reduced glutathione content in affected muscles were higher, whereas mRNA expressions of interleukin-6 and tumor necrosis factor-αwere lower in the HG than those in the HI group. These findings suggest that obese mice pretreated with GLN-supplemented high-fat diet increased circulating EPC percentage, enhanced the antioxidant capacity, and attenuated inflammatory reactions in response to limb ischemia.

Liquid-liquid phase-separating lipid membranes belong to the 2-D Ising universality class. While their in-plane critical behaviors are well studied, how the behaviors modulate out-of-plane interactions is rarely explored, despite its profound implications for biomembranes and 2-D ferromagnets. Here, we examine how the interlayer interaction, manifested as membrane fusion, is affected by the membranes’ critical fluctuations. Remarkably, the critical fluctuations suppress membrane fusion, suggesting a correlation between critical behaviors and interlayer interactions for 2-D Ising systems.

After the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)2] unit has emerged to develop biomimetic DNICs [(NO)2Fe(L)2] as a chemical biology tool for controlled delivery of NO. For example, water-soluble DNIC [Fe2(μ-SCH2CH2OH)2(NO)4] (DNIC-1) was explored for oral delivery of NO to the brain and for the activation of hippocampal neurogenesis. However, the kinetics and mechanism for cellular uptake and intracellular release of NO, as well as the biocompatibility of synthetic DNICs, remain elusive. Prompted by the potential application of NO to dermato-physiological regulations, in this study, cellular uptake and intracellular delivery of DNIC [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-2) and its regulatory effect/biocompatibility toward epidermal cells were investigated. Upon the treatment of DNIC-2 to human fibroblast cells, cellular uptake of DNIC-2 followed by transformation into protein-bound DNICs occur to trigger the intracellular release of NO with a half-life of 1.8 ± 0.2 h. As opposed to the burst release of extracellular NO from diethylamine NONOate (DEANO), the cell-penetrating nature of DNIC-2 rationalizes its overwhelming efficacy for intracellular delivery of NO. Moreover, NO-delivery DNIC-2 can regulate cell proliferation, accelerate wound healing, and enhance the deposition of collagen in human fibroblast cells. Based on the in vitro and in vivo biocompatibility evaluation, biocompatible DNIC-2 holds the potential to be a novel active ingredient for skincare products.

High-fat diet-induced obesity can lead to hepatic insulin resistance (IR) and alter glucose metabolism. The decreased protein expression involved in the PI3K-Akt pathway may enhance hepatic glycogenolysis and gluconeogenesis. Obesity-associated glucose dysregulation and IR are risk factors for the development of peripheral arterial disease. Glutamine (Gln) has immunomodulatory properties and was found to attenuate IR and hyperglycemia in diabetic condition. Thus, in this study we hypothesized that Gln administration modulates hepatic glucose metabolism and improve IR via PI3K-Akt pathway in obese mice with limb ischemia. Mice were divided into a high-fat group (HC), and a high-fat Gln group (HG). Mice in the HC group were fed the high-fat diet for 8 weeks, while the HG group was initially fed the high-fat diet for 4 weeks followed by a high-fat diet with Gln for an additional 4 weeks. Part of the mice in the HC and HG groups were subjected to a limb ischemic operation and were euthanized after the operation. Liver tissues and blood samples were collected for analysis. The results showed that high-fat diet-induced obesity resulted in increased plasma glucose and insulin levels. Also, impairment of hepatic insulin signaling by downregulating PI3K-Akt pathway-associated protein expression was observed. Administration of Gln increased protein expression associated with PI3K-Akt signaling pathway, while reducing G6PC and FOXO1 expression in the hepatocytes that may promote glycogen synthesis and inhibit gluconeogenesis. These findings suggest that obese mice treated with Gln-containing high-fat diet may normalize blood glucose and improve IR in response to limb ischemia.

Enhanced phenotypic diversity increases the likelihood of a population surviving catastrophic conditions. It has been suggested that Hsp90, an essential molecular chaperone in eukaryotes, can suppress (i.e., buffer) or enhance (i.e., potentiate) the effects of genetic variation, enabling organisms to adjust their levels of phenotypic diversity in response to environmental cues. Many Hsp90-interacting proteins are involved in signaling transduction pathways and transcriptional regulation. However, it remains unclear if Hsp90-dependent differential gene expression is common in natural populations. By examining the gene expression profiles of five diverse yeast strains, we identified many genes exhibiting Hsp90-dependent strain-specific differential expression. We employed an analysis pipeline to identify transcription factors (TFs) potentially contributing to variable expression. We found that upon Hsp90 inhibition or heat stress, activities or abundances of Hsp90-dependent TFs varied among strains, resulting in differential strain-specific expression of their target genes, which consequently led to phenotypic diversity. We provide evidence that individual populations can readily display specific Hsp90-dependent gene expression, suggesting that the evolutionary impacts of Hsp90 are widespread in nature.HighlightsHsp90-dependent gene expression varies among different yeast strains.Hsp90 differentially influences transcriptional activity or protein abundances of transcription factors among yeast strains.Differential strain-specific gene expression is correlated with phenotypic variations upon Hsp90 inhibition.Hsp90-mediated strain-specific regulation manifests under environmental stress.

Advances in ultrasound fetal diagnostics and treatment have created a dilemma for doctors and parents: choosing whether to continue with a pregnancy as well as choosing between various treatment options. A multidisciplinary approach has been widely accepted in the management of other prenatally diagnosed anomalies and has shown superior results compared to routine care. We present a retrospective cohort of patients prenatally diagnosed with orofacial clefts who were offered consultation by an expert multidisciplinary team, including: a fetal medicine specialist, an obstetrician, a plastic surgeon, and a case managing nurse. We analyzed factors influencing parents' decision to utilize a consultation service, as well as their decision about pregnancy continuation. Our results suggest that the presence of other anomalies and maternal age heavily influenced the decision about the uptake of consultations. If consulted by the team, parents tended to continue with the pregnancy, even when accounting for fetal gender and maternal age. On the other hand, having a consultation had varying effects depending on the cleft type. The findings suggest that multidisciplinary consultations may be an efficient approach in managing pregnancies complicated by orofacial cleft anomalies; which may help in preventing unnecessary pregnancy terminations and developing a sufficient postnatal care plan.

Insulator-based dielectrophoresis has to date been almost entirely restricted to Newtonian fluids despite the fact that many of the chemical and biological fluids exhibit non-Newtonian characteristics. We present herein an experimental study of the fluid rheological effects on the electroosmotic flow of four types of polymer solutions, i.e., 2000 ppm xanthan gum (XG), 5% polyvinylpyrrolidone (PVP), 3000 ppm polyethylene oxide (PEO), and 200 ppm polyacrylamide (PAA) solutions, through a constriction microchannel under DC electric fields of up to 400 V/cm. We find using particle streakline imaging that the fluid elasticity does not change significantly the electroosmotic flow pattern of weakly shear-thinning PVP and PEO solutions from that of a Newtonian solution. In contrast, the fluid shear-thinning causes multiple pairs of flow circulations in the weakly elastic XG solution, leading to a central jet with a significantly enhanced speed from before to after the channel constriction. These flow vortices are, however, suppressed in the strongly viscoelastic and shear-thinning PAA solution.

Artificial sweeteners are often used by food manufacturers as a low-calorie alternative to sugar. However, an excessive consumption of artificial sweeteners can be harmful to human health. Consequently, their concentration in foods and beverages must be carefully controlled. The current study therefore proposes a microfluidic chromatography detection (MCD) system for the simultaneous concentration determination of two common sweeteners, namely saccharin sodium (SAC) and acesulfame potassium (Ace-K). In the proposed system, the sample is dropped on the MCD chip with a developing solution consisting of DI water, ethyl acetate, acetic acid and ethanol the chip is then placed in a UV microanalysis device. After allowing sufficient time for the developing solution to separate the SAC and Ace-K sweeteners from the interfering substances, the chip is illuminated by a 254-nm ultraviolet lamp and captured by a CMOS camera. Then wirelessly transfer the captured image to a smartphone, where the Ace-K or SAC sweetener concentration is derived using self-developed chromatography analysis app on the smartphone. Results obtained using control samples with known SAC and Ace-K concentrations show that the current MCD system provides a reliable detection performance for both sweeteners over the concentration range of 50 ~ 2000 ppm. Furthermore, the detection results of the concentrations of SAC and Ace-K in 16 commercial food samples are within 6.3% of the results obtained using traditional macroscale HPLC systems.

A novel detection system consisting of a three-dimensional (3-D) sliding hybrid microchip (SHM) and a smart analysis device is presented to determine the phosphorus concentration in whole blood samples. The novelty of the SHM detection system includes filtering whole blood directly into serum, reacting different reagents in stages, performing a closed-type reaction to prevent evaporation of the test sample and uniform heating. The SHM is fabricated on PET and PMMA substrates and incorporates a sample injection zone, a filter paper-strip, two paper-chip reagent zones (reagent A and reagent B), and a detection zone. In the proposed detection method, 6 μL of whole blood sample is injected into the sample chamber and is filtered / separated by the paper-strip as it diffuses toward reagent zone A under the effects of capillary action. After 1 min, the sliding mechanism of the SHM is activated such that reagent zone B is positioned over reagent zone A in the detection/reaction zone. The SHM is then inserted into the smart analysis device and heated at 35°C for 4 min to prompt a modified molybdenum blue reaction. Finally, the blood phosphorus concentration is measured through a colorimetric method performed by a self-developed color analysis app installed on a smartphone. The feasibility of the current SHM detection system is demonstrated by the known control serum phosphorus concentrations ranging from 0.1–9 mg/dL. It is shown that the total R + B + G color intensity of the reaction complex image (Y) is linearly related to the serum phosphorus concentration (X) as Y = -31.502X + 600.740. The coefficient of determination (R2) and detection limit are 0.9936 and 0.06 mg/dL, respectively. The phosphorus concentration detection results obtained using the current SHM system for the whole blood samples of 100 real-world chronic kidney disease (CKD) patients are shown to be in excellent consistent with the detection results acquired through a macroscopic technique. Overall, the current SHM detection system provides a rapid and reliable method to detect the phosphorus concentration in whole blood samples.

Sodium benzoate (SBA) is a widely-used additive for preventing food spoilage and deterioration and extending the shelf life. However, the concentration of SBA must be controlled under safe regulations to avoid damaging human health. Accordingly, this study proposes a microfluidic colorimetric analysis (MCA) system composing of a wax-printed paper-microchip and a self-made smart analysis equipment for the concentration detection of SBA in common foods and beverages. In the presented method, the distilled SBA sample is mixed with NaOH to obtain a nitro compound and the compound is then dripped onto the reaction area of the paper-microchip, which is embedded with two layers of reagents (namely acetophenone and acetone). The paper-microchip is heated at 120 °C for 20 min to cause a colorimetric reaction and the reaction image is then obtained through a CMOS (complementary metal oxide semiconductor) device and transmitted to a cell-phone over a WiFi connection. Finally, use the self-developed RGB analysis software installed on the cell-phone to obtain the SBA concentration. A calibration curve is constructed using SBA samples with known concentrations ranging from 50 ppm (0.35 mM) to 5000 ppm (35 mM). It is shown that the R + G + B value (Y) of the reaction image and SBA concentration (X) are related via Y = −0.034 X +737.40, with a determination coefficient of R2 = 0.9970. By measuring the SBA concentration of 15 commercially available food and beverage products, the actual feasibility of the current MCA system can be demonstrated. The results show that the difference from the measurement results obtained using the macroscale HPLC method does not exceed 6.0%. Overall, the current system provides a reliable and low-cost technique for quantifying the SBA concentration in food and drink products.

Revealing the spatial and temporal distribution of bacteria in organic tea plantations is of great importance to clarify soil- and/or tea plant-associated community. In this study samples were collected from three rhizo-compartments of tea plant during four seasons, which were further subjected to community level physiological profiling and 16S rDNA next generation sequencing. Organic fertilization caused a short-term disturbance on pH, EC, and organic matter content of soil. Three rhizo-compartments harbored distinct bacterial community as revealed by PCA, PCoA and UPGMA analysis. Utilization of six carbon source categories was positively correlated with root surface community while negatively correlated with root interior community. Although there were variations in microbial parameters during four seasons, higher metabolic potential and diversity were observed in soil-associated rhizo-compartments. Bacterial families Gemmataceae, Pedosphaeraceae, and Solibacteraceae were more abundant in soil and root surface, while root interior were dominated by families Acidothermaceae, Burkholderiaceae, Ktedonobacteraceae, and Xanthobacteraceae. It is proposed that Burkholderiaceae and Xanthobacteraceae which dominate in root surface or root interior samples and other poorly studied phylogenetic groups may serve as potential candidates to study their interaction with tea plant.

Nanomaterials have attracted significant attention in biomedical and environmental science in recent years due to their unique thermal, optical, electrical and magnetic properties. The properties of nanomaterials are highly correlated with their size and morphology. Consequently, efficient methods for synthesizing nanomaterials with a consistent size and shape are urgently required. Compared to conventional large-scale synthesis systems, microfluidic systems offer a far better control over the growth, nucleation and reaction conditions. As such, microfluidic synthesis has emerged as a key enabling technology for the rapid, low cost and reliable preparation of nanomaterials with complex properties and functions. This review provides a detailed overview of advances in the microfluidic synthesis technology field over the past five years. The review commences by describing the main microfluidic control mechanisms and microfluidic synthesis of particles. Some of the more common applications of microfluidic synthesized micro and nanomaterials are then introduced, including drug delivery, bioimaging, biosensing, environmental analysis, and cell analysis. The review concludes with a brief overview of the challenges facing the microfluidic synthesis field in the coming years, together with possible research directions aimed at overcoming these challenges.

A microfluidic detection platform is presented for the rapid and low-cost measurement of preservatives in foods. The microfluidic platform consists mainly of an integrated microfluidic reaction chip and a micro-spectrometer detection system. The reaction chip further involves a heater and a micromixer zone for sample/reagent mixing and reaction, and is fabricated on a PMMA substrate using a CO2 laser. The feasibility of the presented platform is confirmed by measuring the concentration of sorbic acid in food samples. In the analysis process, the extracted sample is mixed with Iron(III) reagent and Thiobarbituric acid (TBA) by a gas driving force and a colorimetry reaction (oxidation reaction) of the mixture (pink complex) is then caused by a micro-heater system. The pink complex is driven to the detection chamber of the microfluidic reaction chip, where it is analyzed by the micro-spectrometer system under illumination of a 530 nm (wavelength) LED light source. Finally, the sorbic acid concentration is derived from the measured value using a calibration curve constructed on the basis of seven sorbic acid control samples with known concentrations ranging from 0.02–0.5 g/kg. The results indicated that the sorbic acid concentration detections of the 15 commercial samples obtained using the presented platform differed from the detections obtained using a standard macroscale HPLC method by no more than 7.5%. In a further series of tests, the determination coefficients for benzoic acid, sulfur dioxide and formaldehyde are found to be R2 = 0.9961, 0.9933 and 0.9968, respectively. In other words, the general feasibility of the proposed platform for preservative detection in foods is confirmed.

Electric field is the method of choice in microfluidic devices for precise transport and placement of particles via fluid electroosmosis and particle electrophoresis. However, current studies on particle electrophoresis in microchannels have been focused mainly upon Newtonian fluids though many of the chemical and biological fluids possess non-Newtonian characteristics. Especially lacking is the experimental study of particle electrophoresis in either type of fluids. We report in this work an unprecedented experimental observation that polystyrene particles migrate towards the walls of straight rectangular microchannels in the electroosmotic flow of shear-thinning xanthan gum (XG) solutions. This phenomenon is opposite to the particle focusing along the channel center in our control experiment with the Newtonian base fluid of the XG solutions. It is attributed to a fluid shear thinning-induced lift that overcomes the wall-induced repulsive electrical lift. The parametric effects of the fluid-particle-channel-(electric) field system are systematically investigated.

Recently, the usage of WLCSP (Wafer Level Chip Scale Package) is becoming more widespread, because of WLCSP with virtues in terms of light, thin, short and small aspects [1]. However, it is well known that WLCSP is more critical compared to QFP, QFN and BGA products, regarding die chipping and crack issue, shown in Figure 1a & 1b. Since there is no molding compound to protect the chip, chip will be easily damaged by mechanical force. Especially, during SMT (Surface Mount Technology) process, operators may use the tweezer to pick up devices and cause die chip out phenomenon. Therefore, the purpose of this paper is to study pWLCSP (protected WLCSP), see Figure 2, sample with different molding compound thickness and put into bowl feeder for collision test. For bowl feeder trial run, shown in Figure 3, we will put the dedicated samples with different side wall thickness in terms of 10um, 30um and 90um into the bowl feeder, let samples collide each other, then to check protection ability. In addition, pure Silicon die (WLCSP, no protection) and embedded device will be added into overall DOE (Design of Experiment) plan, we also would like to compare pure Silicon die and embedded samples collision test performance. In summary, it was revealed that thicker side wall thickness pWLCSP sample will be good in bowl feeder trial run, 90um side wall protection thickness and embedded sample are the best as well as we did not find chip out issue after whole experiment. The other key is to control time which sample collision in bowl (within 15min which base on the experiment result), particularly for thin side wall thickness samples.

The sodium/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. Its expression is decreased in individuals with intestinal inflammatory disorders and is correlated with the pathogenesis of disease. The aim of this study was to understand the regulatory mechanism of the SGLT1 gene. Using the trinitrobenzene sulfonic acid-induced mouse models of intestinal inflammation, we observed decreased SGLT1 expression in the inflamed intestine was positively correlated with the mucosal level of epidermal growth factor (EGF) and activated CREB. Overexpression of EGF demonstrated that the effect of EGF on intestinal glucose uptake was primarily due to the increased level of SGLT1. We identified an essential cAMP binding element (CRE) confers EGF inducibility in the human SGLT1 gene promoter. ChIP assay further demonstrated the increased binding of CREB and CBP to the SGLT1 gene promoter in EGF-treated cells. In addition, the EGFR- and PI3K-dependent CREB phosphorylations are involved in the EGF-mediated SGLT1 expression. This is the first report to demonstrate that CREB is involved in EGF-mediated transcription regulation of SGLT1 gene in the normal and inflamed intestine, which can provide potential therapeutic applications for intestinal inflammatory disorders.

In this article, we propose a fabrication technology for preparing curved structures using an electron-beam writing strategy. Oxygen plasma treatment increases the surface roughness of SU-8 polymer, while minimizing the outgassing problem and stabilizing the SU-8 film. Fourier transform infrared spectra of epoxy bond near 915 cm−1 decreased upon increasing the dosage of the electron beam or the treatment time of the oxygen plasma. Convex, concave, and spiral structures were formed successfully using a gradient dosing strategy. The interface between two shot sections was smoothed by the electron scattering effect. The curved profile was fabricated at various curvatures, and characterized using scanning electron microscopy and a profiler. In addition, a spiral structure was fabricated that possesses the advantageous feature of having a small chip area. We discuss a method of characterizing the spiral structure.