Monte Carlo simulation based thinning and calculating method for noninvasive blood glucose sensing by near-infrared spectroscopy

Previous results show that the floating reference theory(FRT)is an effective tool to reduce the infuence of interference factors on noninvasive blood glucose sensing by near infrared spectros-copy(NIRS).It is the key to measure the floating reference point(FRP)precisely for the application of FRT.Monte Carlo(MC)simulation has been introduced to quantitatively in-vestigate the effects of positioning errors and light source drifts on measuring FRP.In this article,thinning and calculating method(TCM)is proposed to quantify the positioning error.Mean-while,the normalization process(NP)is developed to significantly reduce the error induced by light source drift.The results according to TCM show that 7 purm deviations in positioning can generate about 10.63%relative error in FRP.It is more noticeable that 1%fluctuation in light source intensity may lead to 12.21%relative errors.Gratifyingly,the proposed NP model can effectively reduce the error caused by light source drift.Therefore,the measurement system for FRPs must meet that the positioning error is less than 7 purm,and the light source drift is kept within 1%.Furthermore,an improvement for measurement system is proposed in order to take advantage of the NP model.

Large-scale manufacturing of functional single-atom ink for convenient glucose sensing

Printing techniques hold great potential in the manufacture of electronics such as sensors,micro-supercapacitors,and flexible electronics.However,developing large-scale functional conductive inks with appropriate rheological properties and active components still remains a challenge.Herein,through optimizing the formulations of ink,iron single sites supported N-doped carbon black(Fe_(1)-NC)inks can serve as both conductive electrodes and high-reactive catalysts to realize convenient glucose detection,which pronouncedly reduces the dosage of enzyme and simplifies the sensors preparation.In detail,utilizing in-situ pyrolysis method,Fe_(1)-NC single-atom catalysts(SACs)are prepared in bulk(dekagram-level).The batched Fe_(1)-NC SACs materials can be uniformly mixed with modulated ink to realize the screen printing with high resolution and uniformity.Also,the whole scalable preparation and ink-functional process can be extended to various metals(including Co,Ni,Cu,and Mn).The introduction of highly active Fe_(1)-NC sites reduces the amount of enzyme used in glucose detection by at least 50%,contributing to the cost reduction of sensors.The strategy in harnessing the SACs onto the carbon inks thus provides a broad prospect for the low-cost and large-scale printing of sensitive sensing devices.

Facile Semiconductor p-n Homojunction Nanowires with Strategic p-Type Doping Engineering Combined with Surface Reconstruction for Biosensing Applications

Photosensors with versatile functionalities have emerged as a cornerstone for breakthroughs in the future optoelectronic systems across a wide range of applications.In particular,emerging photoelectrochemical(PEC)-type devices have recently attracted extensive interest in liquid-based biosensing applications due to their natural electrolyte-assisted operating characteristics.Herein,a PEC-type photosensor was carefully designed and constructed by employing gallium nitride(GaN)p-n homojunction semiconductor nanowires on silicon,with the p-GaN segment strategically doped and then decorated with cobalt-nickel oxide(CoNiO_(x)).Essentially,the p-n homojunction configuration with facile p-doping engineering improves carrier separation efficiency and facilitates carrier transfer to the nanowire surface,while CoNiO_(x)decoration further boosts PEC reaction activity and carrier dynamics at the nanowire/electrolyte interface.Consequently,the constructed photosensor achieves a high responsivity of 247.8 mA W^(-1)while simultaneously exhibiting excellent operating stability.Strikingly,based on the remarkable stability and high responsivity of the device,a glucose sensing system was established with a demonstration of glucose level determination in real human serum.This work offers a feasible and universal approach in the pursuit of high-performance bio-related sensing applications via a rational design of PEC devices in the form of nanostructured architecture with strategic doping engineering.

Microarrow sensor array with enhanced skin adhesion for transdermal continuous monitoring of glucose and reactive oxygen species

Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.

Development and characterization of a microfluidic glucose sensing system based on an enzymatic microreactor and chemiluminescence detection

Chemiluminescence detection was developed as an alternative to amperometric detection for glucose analysis in a portable, microfluidicsbased continuous glucose monitoring system. Amperometric detection allows easy determination of hydrogen peroxide, a product of the glucose oxidasecatalyzed reaction of glucose with oxygen, by oxidation at a microelectrode. However, （micro）electrodes in direct contact with physiological sample are subject to electrode fouling, which leads to signal drift, decreased reproducibility and shortened detector lifetimes. Moreover, there are a few species present in the body （e.g. ascorbic acid, uric acid） which can undergo oxidation at the same applied potential as hydrogen peroxide. These species can thus inter- fere with the glucose measurement, reducing detection specificity. The rationale for exploring chemiluminescence as opposed to amperometric detection is thus to attempt to improve the lifetime and reproducibility of glucose analysis for monitoring purposes, while reducing interference caused by other chemicals in the body. The study reported here represents a first step in this direction, namely the realization of a microfluidic device with integrated silicon photodiode for chemiluminescence detection of glucose. This microflow device uses a chaotic mixing approach to perform enzymatic conversion of glucose, followed by reaction of the hydrogen peroxide produced with luminol to produce light at 425 nm. The chemil reaction is catalyzed by horseradish peroxidase in the presence of iodophenol. The performance of the fabricated chip was characterized to establish optimal reaction conditions with respect to sample and reagent flow rates, pH, and concentrations. A linear calibra- tion curve was obtained for current response as a function of glucose concentration in the clinically relevant range between 2 and 10 mM, with a sensitivity of 39 pA/mM （R = 0.9963, one device, n = 3） and a limit of detection of 230 ktM （S/N - 3）.

Promoted Non-enzymatic Glucose Sensor Based on Synergistic Effect of Hydrothermal Synthesized Ni(OH)_(2)-Graphene Nanocomposite

Although glucose electrochemical sensors based on enzymes play a dominant role in market,their stability remains a problem due to the inherent nature of enzymes.Therefore,glucose sensors that are independent on enzymes have attracted more attention for the development of stable detection devices.Here we present an enzyme-free glucose sensor based on Ni(OH)_(2)and reduced graphene oxide(rGO).The as-fabricated sensor still exhibits excellent electrocatalytic activity for detecting glucose under enzyme independent conditions.The enhanced catalytic performance may due to synergistic effect as follows:(i)the interaction between the Ni2+andπelectron of graphene induces the formation of theβ-phase Ni(OH)_(2)with higher catalytic activity;(ii)the frozen dry process works as a secondary filtration,getting rid of poorly formed Ni(OH)_(2)particles with low catalytic activity;(iii)the rGO network with good conductivity provides a good electronic pathway for promoting electron transfer to reduce the response time.Based on the synergistic effect,the sensor exhibits a wide linear detection range from 0.2µmol/L to 1.0µmol/L and a low detection limit(0.1µmol/L,S/N=3).The excellent detection performance,as well as the easy and low-cost preparation method,suggests the promising applicability of the sensor in the glucose detection market.

Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK

When glucose is replete,mammalian/mechanistic target of rapamycin complex 1(mTORC1)is active and anchored to the lysosomal surface via the two GTPases,Ras-related GTPase(RAG)and Ras homolog enriched in brain(Rheb),which are regulated by Ragulator and tuberous sclerosis complex 2(TSC2),respectively.When glucose is low,aldolase senses low fructose-1,6-bisphosphate level and promotes the translocation of AXIN−liver kinase B1(LKB1)to the lysosomal surface,which leads to the activation of AMP-activated protein kinase(AMPK)and the inhibition of RAGs,sundering mTORC1 from the lysosome and causing its inactivation.AMPK can also inactivate mTORC1 by phosphorylating Raptor and TSC2.However,the hierarchy of AXIN-and AMPK-mediated inhibition of mTORC1 remains poorly defined.Here,we show that AXIN translocation does not require AMPK expression or activity.In glucose starvation conditions,knockout of AXIN extended the half-life of mTORC1 inhibition from 15 to 60 min,whereas knockout of AMPK only extended it to 30 min.RAGBGTP(constitutively active RAGB)almost entirely blocked the lysosomal dissociation and inhibition of mTORC1 under glucose starvation,but it did not inhibit AMPK,indicating that under these conditions,it is AXIN lysosomal translocation that inhibits mTORC1,and it does so via inhibition of RAGs.5-aminoimidazole-4-carboxamide ribonucleoside(AICAR),a mimetic of AMP,which activates both cytosolic AMPK and lysosomal AMPK,fully inhibited mTORC1 even when it is stably anchored to the lysosome by RAGBGTP,whereas glucose starvation mildly inhibited such anchored mTORC1.Together,we demonstrate that the lysosomal translocation of AXIN plays a primary role in glucose starvation-triggered inhibition of mTORC1 by inhibiting RAGs,and that AMPK activity inhibits mTORC1 through phosphorylating Raptor and TSC2,especially under severe stress.

Plasmonic organic electrochemical transistors for enhanced sensing

Organic electrochemical transistors(OECTs)have been hailed as highly sensitive biomolecular sensors among organic electronic devices due to their superior stability in an aqueous environment and high transconductance.At the same time,plasmon based sensors are known to provide high sensitivity for biosensing due to the highly localized plasmonic field.Here we report a plasmonic OECT(POET)device that synchronizes the advantages of OECTs and plasmonic sensors on a single platform.The platform is fabricated by a simple,cost-effective,and high-throughput nanoimprinting process,which allows plasmonic resonance peak tuning to a given visible wavelength of interest for versatile biosensing.With glucose sensing as proof,a five-times sensitivity enhancement is obtained for POET compared to a regular(non-plasmonic)OECT.Thus,the POET paves the way to a new paradigm of optoelectronic sensors that combines the inherent high sensitivity of OECTs and localized plasmonic field to sense a vast realm of biomolecules.

Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver

Mitochondria-associated endoplasmic reticulum membranes(MAM)play a key role in mitochondrial dynamics and function and in hepatic insulin action.Whereas mitochondria are important regulators of energy metabolism,the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown.In this study,we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse liver.Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo.Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A(PP-PP2A)pathway,induced mitochondria fission,and impaired respiration.Blocking MAM reduction counteracted glucose-induced mitochondrial alterations.Furthermore,disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function.This glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice,both characterized by chronic disruption of MAM integrity,mitochondrial fission,and altered mitochondrial respiration.These data indicate that MAM contribute to the hepatic glucose-sensing system,allowing regulation of mitochondria dynamics and function during nutritional transition.Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance.

Ternary Pd-Ni-P nanoparticle-based nonenzymatic glucose sensor with greatly enhanced sensitivity achieved through active-site engineering

We develop a unique ternary Pd-Ni-P nanocatalyst for the sensitive enzyme- free electrooxidation detection of glucose under alkaline conditions. By reducing the distance between the Pd and Ni active sites in the Pd-Ni-P nanoparticles （NPs） via atom engineering, the catalyst structure is transformed from Pd@Ni-P dumbbells into spherical NPs, greatly enhancing the catalyst sensitivity. The glassy carbon electrode modified with Pd-Ni-P ternary NPs, which behaves as an efficient nonenzymatic glucose sensor, offers excellent electrocatalytic performance with a high sensitivity of 1,136 μA·mM^-1·cm^-2, a short response time of 2 s, a wide linear range of 0.5 μM to 10.24 mM, a low limit of detection of 0.15 μM （signal-to-noise ratio = 3）, and good selectivity and reproducibility. Moreover, owing to its superior catalytic performance, the Pd-Ni-P modified electrode has excellent reliability for glucose detection in real samples of human serum. Our study provides a promising alternative strategy for designing and constructing high-performance multicomponent nanocatalyst-based sensors.

Enhanced Electroactivity of Facet-Controlled Co3O4 Nanocrystals for Enzymeless Biosensing

In this work, we report enhanced electroactivity of Co304 nanocrystals （nanocubes, NCs and truncated nano-octahedra, TNO） on the exposed {111} facets as compared to the {001} facets in relation to the surface density and the activity of the octahedral Com species. Transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy were em- ployed to characterize the crystal facets and materials properties. The enhanced electroactivity of {111 } crystal facets was evaluated by cyclic voltammetry and amperometric titration. Our results indicate that the {111 } facets in TNO has a better electroactivity for enzymeless glucose sensing with a decent glucose sensitivity of 32.54 μA （mmol/L）-1 cm-2.

The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling and metabolic control

Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWlISNF chromatin.remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological sigrials. The ATP-dependent SWl/SNF ing complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different m^abolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.