Machine learning-enabled hyperspectral approaches for structural characterization of precooked noodles during refrigerated storage.

The structural features of precooked noodles during refrigerated storage were non-destructively characterized using hyperspectral imaging (HSI) technology along with conventional analytical methods. The precooked noodles displayed a more rigid texture and restricted water mobility over the storage period, derived from the recrystallization of starch. Dimensionality reduction techniques revealed robust correlations between the storage duration and HSI absorbance of the noodles, and from their loading plots, the specific peaks of the noodles related to their structural changes were identified at wavelengths of around 1160 and 1400 nm. The strong relationships between the HSI results of the noodles and their storage period/texture were confirmed by training four machine learning models on the HSI data. In particular, the support vector algorithm displayed the best prediction performance for classifying precooked noodles by storage period (98.3% accuracy) and for predicting the noodle texture (R2 = 0.914).

Lutein fortification of wheat bread with marigold powder: impact on rheology, water dynamics, and structure.

BACKGROUND: Demands for foods conducive to eye health have been on the increase in the global healthcare sector. Marigold powder as a major source of lutein was utilized to produce lutein-fortified breads for ocular health. The physicochemical characteristics of the doughs and breads were investigated in terms of rheology, water mobility, and protein secondary structures. RESULTS: The incorporation of marigold powder decreased the water absorption of doughs without significantly altering thermomechanical properties. With a range of fortification levels (1-3%), marigold powder led to decreased storage and loss modulus of doughs by weakening their gluten network, which was supported by their T2 relaxation times. The resistance of the doughs weakened with increasing levels of marigold powder, while their extensibilities significantly incremented. Fourier transform infrared spectral deconvolution revealed the changes in wheat protein structures upon marigold powder incorporation, in which the proportion of ß-turn increased at the expense of ß-sheet ratio. The breads with marigold powder displayed increased specific volume from 4.034 to 4.368 mL g-1 , accompanied by softer textures. The baking process led to heat-induced losses in lutein concentration of less than 10% within the crumb and approximately 30% in the crust. CONCLUSION: The use of marigold powder induced changes in protein secondary structure and extensional features of doughs, contributing to increased loaf volume and softer texture. Overall, this study provides fundamental information on the rheological and structural effects of marigold powder in a wheat bread system, consequently encouraging the food industry to utilize marigold power as a functional food ingredient. © 2023 Society of Chemical Industry.

An A-ring substituted evodiamine derivative with potent anticancer activity against human non-small cell lung cancer cells by targeting heat shock protein 70.

The heat shock protein (HSP) system is essential for the conformational stability and function of several proteins. Therefore, the development of efficacious HSP-targeting anticancer agents with minimal toxicity is required. We previously demonstrated that evodiamine is an anticancer agent that targets HSP70 in non-small cell lung cancer (NSCLC) cells. In this study, we synthesized a series of evodiamine derivatives with improved efficacy and limited toxicity. Among the 14 evodiamine derivatives, EV408 (10-hydroxy-14-methyl-8,13,13b,14-tetrahydroindolo[2',3':3,4]pyrido[2,1-b]quinazolin-5(7H)-one) exhibited the most potent inhibitory effects on viability and colony formation under anchorage-dependent and -independent culture conditions in various human NSCLC cells, including those that are chemoresistant, by inducing apoptosis. In addition, EV408 suppressed the cancer stem-like cell (CSC) population of NSCLC cells and the expression of stemness-associated markers. Mechanistically, EV408 inhibited HSP70 function by directly binding and destabilizing the HSP70 protein. Furthermore, EV408 significantly inhibited the growth of NSCLC cell line tumor xenografts without overt toxicity. Additionally, EV408 had a negligible effect on the viability of normal cells. These results suggest the potential of EV408 as an efficacious HSP70-targeting evodiamine derivative with limited toxicity that inhibits both non-CSC and CSC populations in NSCLC.

High-throughput genetic engineering tools for regulating gene expression in a microbial cell factory.

With the rapid advances in biotechnological tools and strategies, microbial cell factory-constructing strategies have been established for the production of value-added compounds. However, optimizing the tradeoff between the biomass, yield, and titer remains a challenge in microbial production. Gene regulation is necessary to optimize and control metabolic fluxes in microorganisms for high-production performance. Various high-throughput genetic engineering tools have been developed for achieving rational gene regulation and genetic perturbation, diversifying the cellular phenotype and enhancing bioproduction performance. In this paper, we review the current high-throughput genetic engineering tools for gene regulation. In particular, technological approaches used in a diverse range of genetic tools for constructing microbial cell factories are introduced, and representative applications of these tools are presented. Finally, the prospects for high-throughput genetic engineering tools for gene regulation are discussed.

Discovery of GSK3ß Inhibitors through In Silico Prediction-and-Experiment Cycling Strategy, and Biological Evaluation.

Direct inhibitors of glycogen synthase kinase 3ß (GSK3ß) have been investigated and reported for the past 20 years. In the search for novel scaffold inhibitors, 3000 compounds were selected through structure-based virtual screening (SBVS), and then high-throughput enzyme screening was performed. Among the active hit compounds, pyrazolo [1,5-a]pyrimidin-7-amine derivatives showed strong inhibitory potencies on the GSK3ß enzyme and markedly activated Wnt signaling. The result of the molecular dynamics (MD) simulation, enhanced by the upper-wall restraint, was used as an advanced structural query for the SBVS. In this study, strong inhibitors designed to inhibit the GSK3ß enzyme were discovered through SBVS. Our study provides structural insights into the binding mode of the inhibitors for further lead optimization.

Targeting epidermal growth factor receptor in paclitaxel-resistant human breast and lung cancer cells with upregulated glucose-6-phosphate dehydrogenase.

BACKGROUND: Chemoresistance is a major obstacle to the successful treatment of triple-negative breast cancer (TNBC) and non-small-cell lung cancer (NSCLC). Therapeutic strategies to overcome chemoresistance are necessary to improve the prognosis of patients with these cancers. METHODS: Paclitaxel-resistant TNBC and NSCLC sublines were generated through continuous paclitaxel treatment over 6 months. The mechanistic investigation was conducted using MTT assay, LC/MS-based metabolite analysis, flow cytometry, western blot analysis, real-time PCR and tumour xenograft experiments. RESULTS: Glucose-6-phosphate dehydrogenase (G6PD) expression along with an increase in 3-phosphoglycerates and ribulose-5-phosphate production was upregulated in paclitaxel-resistant cells. Blockade of G6PD decreased viability of paclitaxel-resistant cells in vitro and the growth of paclitaxel-resistant MDA/R xenograft tumours in vivo. Mechanistically, activation of the epidermal growth factor receptor (EGFR)/Akt pathway mediates G6PD expression and G6PD-induced cell survival. Blockade of the EGFR pathway inhibited G6PD expression and sensitised those paclitaxel-resistant cells to paclitaxel treatment in vitro and in vivo. Analysis of publicly available datasets revealed an association between G6PD and unfavourable clinical outcomes in patients with breast or lung cancer. CONCLUSIONS: EGFR signaling-mediated G6PD expression plays a pivotal role in paclitaxel resistance, highlighting the potential of targeting EGFR to overcome paclitaxel resistance in TNBC and NSCLC cells overexpressing G6PD.

Portable Seawater Desalination System for Generating Drinkable Water in Remote Locations.

A portable seawater desalination system would be highly desirable to solve water challenges in rural areas and disaster situations. While many reverse osmosis-based portable desalination systems are already available commercially, they are not adequate for providing reliable drinking water in remote locations due to the requirement of high-pressure pumping and repeated maintenance. We demonstrate a field-deployable desalination system with multistage electromembrane processes, composed of two-stage ion concentration polarization and one-stage electrodialysis, to convert brackish water and seawater to drinkable water. A data-driven predictive model is used to optimize the multistage configuration, and the model predictions show good agreement with the experimental results. The portable system desalinates brackish water and seawater (2.5-45 g/L) into drinkable water (defined by WHO guideline), with the energy consumptions of 0.4-4 (brackish water) and 15.6-26.6 W h/L (seawater), respectively. In addition, the process can also reduce suspended solids by at least a factor of 10 from the source water, resulting in crystal clear water (<1 NTU) even from the source water with turbidity higher than 30 NTU (i.e., cloudy seawater by the tide). We built a fully integrated prototype (controller, pumps, and battery) packaged into a portable unit (42 × 33.5 × 19 cm3, 9.25 kg, and 0.33 L/h production rate) controlled by a smartphone, tested for battery-powered field operation. The demonstrated portable desalination system is unprecedented in size, efficiency, and operational flexibility. Therefore, it could address unique water challenges in remote, resource-limited regions of the world.

A novel C-terminal heat shock protein 90 inhibitor that overcomes STAT3-Wnt-ß-catenin signaling-mediated drug resistance and adverse effects.

Rationale: The heat shock protein (Hsp) system plays important roles in cancer stem cell (CSC) and non-CSC populations. However, limited efficacy due to drug resistance and toxicity are obstacles to clinical use of Hsp90 inhibitors, suggesting the necessity to develop novel Hsp90 inhibitors overcoming these limitations. Methods: The underlying mechanism of resistance to Hsp90 inhibitors was investigated by colony formation assay, sphere formation assay, western blot analysis, and real-time PCR. To develop anticancer Hsp90 inhibitors that overcome the signal transducer and activator of transcription 3 (STAT3)-mediated resistance, we synthesized and screened a series of synthetic deguelin-based compounds in terms of inhibition of colony formation, migration, and viability of non-small cell lung cancer (NSCLC) cells and toxicity to normal cells. Regulation of Hsp90 by the selected compound NCT-80 [5-methoxy-N-(3-methoxy-4-(2-(pyridin-3-yl)ethoxy)phenyl)-2,2-dimethyl-2H-chromene-6-carboxamide] was investigated by immunoprecipitation, drug affinity responsive target stability assay, binding experiments using ATP-agarose beads and biotinylated drug, and docking analysis. The antitumor, antimetastatic, and anti-CSC effects of NCT-80 were examined in vitro and in vivo using various assays such as MTT, colony formation, and migration assays and flow cytometric analysis and tumor xenograft models. Results: We demonstrated a distinct mechanism in which Hsp90 inhibitors that block N-terminal ATP-binding pocket causes transcriptional upregulation of Wnt ligands through Akt- and ERK-mediated activation of STAT3, resulting in NSCLC cell survival in an autocrine or paracrine manner. In addition, NCT-80 effectively reduced viability, colony formation, migration, and CSC-like phenotypes of NSCLC cells and their sublines with acquired resistance to anticancer drugs by inducing apoptosis and inhibiting epithelial-mesenchymal transition and the growth of NSCLC patient-derived xenograft tumors without overt toxicity. With regards to mechanism, NCT-80 directly bound to the C-terminal ATP-binding pocket of Hsp90, disrupting the interaction between Hsp90 and STAT3 and degrading STAT3 protein. Moreover, NCT-80 inhibited chemotherapy- and EGFR TKI-induced programmed cell death ligand 1 expression and potentiated the antitumor effect of chemotherapy in the LLC-Luc allograft model. Conclusions: These data indicate the potential of STAT3/Wnt signaling pathway as a target to overcome resistance to Hsp90 inhibitors and NCT-80 as a novel Hsp90 inhibitor that targets both CSCs and non-CSCs in NSCLC.

Comprehensive Electrokinetic-Assisted Separation of Oil Emulsion with Ultrahigh Flux.

Many industries have a significant but largely unmet need for efficient and high-flux emulsion separation, particularly for nanoemulsions. Conventional separation membranes rely on size-based separation mainly utilizing a sieving mechanism plus a wetting phenomenon, resulting in a dramatic trade-off between separation efficiency and separation flux. Herein we address this challenge by adapting electrokinetics to membrane-based separation, using a charge-based mechanism capable of separating even nanoemulsions with a demonstrated separation efficiency of >99% and ultrahigh flux up to 40 000 L/H·m2. Our device arrests nano-oil droplets, allowing them to coalesce into larger droplets which are then able to be filtered by coarser membranes. This hybrid technology makes electrokinetic-assisted filtration scalable and commercially viable and allows for a better understanding of the multiphysics underlying dynamic separation.

Implementation of a Computerized Provider Order Entry System in a Pediatric Hospital in Canada.

The Centre Hospitalier Universitaire Sainte-Justine (Montreal, Canada) is a pediatric academic tertiary hospital that has begun the implementation of a commercial computerized provider order entry system (CPOE) in October 2019. The objectives of this paper are 1) to estimate the impact of the CPOE system on medication errors, and 2) to identify vulnerability issues related to the configuration of the CPOE system's design. Using a pre-post implementation methodology measuring medication errors captured by clinical pharmacists revealed that the implementation of a CPOE has eliminated all prescription conformity (e.g., missing fields) and legibility errors. Pharmacists have continued to detect medication errors, especially inappropriate dosing instructions, and to intervene in similar clinical situations (medication reconciliation, deprescribing, adjusting orders). Additionally, the vulnerability analysis, based on typical clinical order test cases in an inpatient pediatric setting, highlighted the need to configure a clinical decision support system that can identify inappropriate dosing instructions for pediatric patients.

Transparent Body-Attachable Multifunctional Pressure, Thermal, and Proximity Sensor and Heater.

A multifunctional sensor capable of simultaneous sensing of temperature, pressure, and proximity has been developed. This transparent and body-attachable device is also capable of providing heat under low voltage. The multi-sensor consists of metal fibers fabricated by electrospinning and electroplating. The device comprises randomly deposited metal fibers, which not only provide heating but also perform as thermal and proximity sensors, and orderly aligned metal fibers that act as a pressure sensor. The sensor is fabricated by weaving straight rectangular electrodes on a transparent substrate (a matrix). The sensitivity is readily enhanced by installing numerous matrices that facilitate higher sensing resolution. The convective heat transfer coefficient of the heater is h = 0.014 W·cm-2·°C-1. The temperature coefficient of resistivity (TCR) and pressure sensitivity (ηP) are 0.038 °C-1 and 5.3 × 10-3 kPa-1, respectively. The superior sensitivity of the device is confirmed via quantitative comparison with similar devices. This multifunctional device also has a superior convective heat transfer coefficient than do other heaters reported in the literature.

An on-demand micro/nano-convertible channel using an elastomeric nanostructure for multi-purpose use.

Recently, nanochannels have been widely adopted in microfluidic systems, especially for biosensing and bio-concentrators. Here, we report an on-demand micro/nano-convertible channel, which consists of a simple configuration of elastic nanostructure underneath a single microchannel. By the degree of pressure applied by a pushrod, the microchannel starts to compress into a size-tunable micro- or nano-porous channel. In this approach, under an electric field, we have successfully derived the electrokinetic characteristics of three different regimes: (1) microchannel regime, (2) microporous regime, and (3) nanochannel regime. Utilizing the practical advantage of the transition between regimes with its low cost and easy integration, we demonstrate the pre-concentration and label-free sensing of DNA using a single on-demand convertible channel. Moreover, we demonstrate an ionic diode by applying asymmetric pressure on the elastic nanostructure to create an asymmetric geometry. We believe that the on-demand convertible channel holds potential for promising applications in bioanalytical and iontronic fields.

Wearable transparent thermal sensors and heaters based on metal-plated fibers and nanowires.

Electrospun metal-plated nanofibers and supersonically sprayed nanowires were used to fabricate hybrid films exhibiting a superior low sheet resistance of 0.18 Ω sq-1, a transparency of 91.1%, and a figure-of-merit of 2.315 Ω-1. The films are suitable to serve as thermal sensors and heaters. Such hybrid transparent conducting films are highly flexible and thus wearable. They can be used as body-temperature monitors and heaters. The employed hybrid approach improved the sheet resistance diminishing it to a minimum, while maintaining transparency. In addition, the low sheet resistance of the films facilitates their powering with a low-voltage battery and thus, portability. The thermal sensing and heating capabilities were demonstrated for such films with various sheet resistances and degrees of transparency. The temperature sensing was achieved by the resistance change of the film; the resistance value was converted back to temperature. The sensing performance increased with the improvement in the sheet resistance. The temperature coefficient of resistivity was TCR = 0.0783 K-1. The uniform distribution of the metal-plated nanofibers and nanowires resulted in a uniform Joule heating contributing to an efficient convection heat transfer from the heaters to the surrounding, demonstrated by an improved convective heat transfer coefficient.

Corrigendum: Purification of High Salinity Brine by Multi-Stage Ion Concentration Polarization Desalination.

This corrects the article DOI: 10.1038/srep31850.

System Modeling of a MEMS Vibratory Gyroscope and Integration to Circuit Simulation.

Recently, consumer applications have dramatically created the demand for low-cost and compact gyroscopes. Therefore, on the basis of microelectromechanical systems (MEMS) technology, many gyroscopes have been developed and successfully commercialized. A MEMS gyroscope consists of a MEMS device and an electrical circuit for self-oscillation and angular-rate detection. Since the MEMS device and circuit are interactively related, the entire system should be analyzed together to design or test the gyroscope. In this study, a MEMS vibratory gyroscope is analyzed based on the system dynamic modeling; thus, it can be mathematically expressed and integrated into a circuit simulator. A behavioral simulation of the entire system was conducted to prove the self-oscillation and angular-rate detection and to determine the circuit parameters to be optimized. From the simulation, the operating characteristic according to the vacuum pressure and scale factor was obtained, which indicated similar trends compared with those of the experimental results. The simulation method presented in this paper can be generalized to a wide range of MEMS devices.

Re-adjusting the cut-off score of the Korean version of the Childhood Autism Rating Scale for high-functioning individuals with autism spectrum disorder.

AIM: The current cut-off score of the Korean version of the Childhood Autism Rating Scale (K-CARS) does not seem to be sensitive enough to precisely diagnose high-functioning autism. The aim of this study was to identify the optimal cut-off score of K-CARS for diagnosing high-functioning individuals with autism spectrum disorders (ASD). METHODS: A total of 329 participants were assessed by the Korean versions of the Autism Diagnostic Interview - Revised (K-ADI-R), Autism Diagnostic Observation Schedule (K-ADOS), and K-CARS. IQ and Social Maturity Scale scores were also obtained. RESULTS: The true positive and false negative rates of K-CARS were 77.2% and 22.8%, respectively. Verbal IQ (VIQ) and Social Quotient (SQ) were significant predictors of misclassification. The false negative rate increased to 36.0% from 19.8% when VIQ was >69.5, and the rate increased to 44.1% for participants with VIQ > 69.5 and SQ > 75.5. In addition, if SQ was >83.5, the false negative rate increased to 46.7%, even if the participant's VIQ was ≤69.5. Optimal cut-off scores were 28.5 (for VIQ ≤ 69.5 and SQ ≤ 75.5), 24.25 (for VIQ > 69.5 and SQ > 75.5), and 24.5 (for SQ > 83.5), respectively. CONCLUSION: The likelihood of a false negative error increases when K-CARS is used to diagnose high-functioning autism and Asperger's syndrome. For subjects with ASD and substantial verbal ability, the cut-off score for K-CARS should be re-adjusted and/or supplementary diagnostic tools might be needed to enhance diagnostic accuracy for ASD.

Purification of High Salinity Brine by Multi-Stage Ion Concentration Polarization Desalination.

There is an increasing need for the desalination of high concentration brine (>TDS 35,000 ppm) efficiently and economically, either for the treatment of produced water from shale gas/oil development, or minimizing the environmental impact of brine from existing desalination plants. Yet, reverse osmosis (RO), which is the most widely used for desalination currently, is not practical for brine desalination. This paper demonstrates technical and economic feasibility of ICP (Ion Concentration Polarization) electrical desalination for the high saline water treatment, by adopting multi-stage operation with better energy efficiency. Optimized multi-staging configurations, dependent on the brine salinity values, can be designed based on experimental and numerical analysis. Such an optimization aims at achieving not just the energy efficiency but also (membrane) area efficiency, lowering the true cost of brine treatment. ICP electrical desalination is shown here to treat brine salinity up to 100,000 ppm of Total Dissolved Solids (TDS) with flexible salt rejection rate up to 70% which is promising in a various application treating brine waste. We also demonstrate that ICP desalination has advantage of removing both salts and diverse suspended solids simultaneously, and less susceptibility to membrane fouling/scaling, which is a significant challenge in the membrane processes.

Surface display expression of Bacillus licheniformis lipase in Escherichia coli using Lpp'OmpA chimera.

The lipase from Bacillus licheniformis ATCC14580 was displayed on the cell surface of Escherichia coli using Lpp'OmpA as the anchoring protein. The expressed Lpp'OmpA-lipase fusion protein has a molecular weight of approximately 35 kDa, which was confirmed by SDS-PAGE and western blot analysis. The Lpp'OmpA-lipase fusion protein was located on the cell surface, as determined by immunofluorescence confocal microscopy and flow cytometry. The enzyme activity of the surface-displayed lipase showed clear halo around the colony. The cell surface-displayed lipase showed the highest activity of 248.12 ± 9.42 U/g (lyophilized cell) at the optimal temperature of 37°C and pH 8.0. The enzyme exhibited the highest activity toward the substrate p-nitrophenyl caprylate (C8). These results suggest that E. coli, which displayed the lipase on its surface, could be used as a whole cell biocatalyst.

Ultra-high-aspect-orthogonal and tunable three dimensional polymeric nanochannel stack array for BioMEMS applications.

Nanofabrication technologies have been a strong advocator for new scientific fundamentals that have never been described by traditional theory, and have played a seed role in ground-breaking nano-engineering applications. In this study, we fabricated ultra-high-aspect (∼10(6) with O(100) nm nanochannel opening and O(100) mm length) orthogonal nanochannel array using only polymeric materials. Vertically aligned nanochannel arrays in parallel can be stacked to form a dense nano-structure. Due to the flexibility and stretchability of the material, one can tune the size and shape of the nanochannel using elongation and even roll the stack array to form a radial-uniformly distributed nanochannel array. The roll can be cut at discretionary lengths for incorporation with a micro/nanofluidic device. As examples, we demonstrated ion concentration polarization with the device for Ohmic-limiting/overlimiting current-voltage characteristics and preconcentrated charged species. The density of the nanochannel array was lower than conventional nanoporous membranes, such as anodic aluminum oxide membranes (AAO). However, accurate controllability over the nanochannel array dimensions enabled multiplexed one microstructure-on-one nanostructure interfacing for valuable biological/biomedical microelectromechanical system (BioMEMS) platforms, such as nano-electroporation.