Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy.

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO2 Detection.

Monitoring of carbon dioxide (CO2) body levels is crucial under several clinical conditions (e.g., human intensive care and acid-base disorders). To date, painful and risky arterial blood punctures have been performed to obtain discrete CO2 measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO2, these are currently limited to benchtop devices, requiring trained personnel, being tedious, and providing punctual information, among other disadvantages. To the best of our knowledge, the literature and market lack a wearable device for real-time, on-body monitoring of CO2. Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO2-MN, comprising a combination of potentiometric pH- and carbonate (CO32-)-selective electrodes together with the reference electrode. The CO2-MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO32- concentrations directly into the interstitial fluid (ISF). The levels for the pH-CO32- tandem are then used to estimate the PCO2 in the ISF. Assessing the response of each individual MN, we found adequate response time (t95 < 5s), sensitivity (50.4 and -24.6 mV dec-1 for pH and CO32-, respectively), and stability (1.6 mV h-1 for pH and 2.1 mV h-1 for CO32-). We validated the intradermal measurements of CO2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO2-MN wearable device for on-body measurements. A good correlation between ISF and blood CO2 concentrations was observed, demonstrating the high potential of the developed MN sensing technology as an alternative to blood-based analysis in the near future. Moreover, these results open new horizons in the noninvasive, real-time monitoring of CO2 as well as other clinically relevant gases.

Fully Integrated Wearable Device for Continuous Sweat Lactate Monitoring in Sports.

The chemical digitalization of sweat using wearable sensing interfaces is an attractive alternative to traditional blood-based protocols in sports. Although sweat lactate has been claimed to be a relevant biomarker in sports, an analytically validated wearable system to prove that has not yet been developed. We present a fully integrated sweat lactate sensing system applicable to in situ perspiration analysis. The device can be conveniently worn in the skin to monitor real-time sweat lactate during sports, such as cycling and kayaking. The novelty of the system is threefold: advanced microfluidics design for sweat collection and analysis, an analytically validated lactate biosensor based on a rational design of an outer diffusion-limiting membrane, and an integrated circuit for signal processing with a custom smartphone application. The sensor covering the range expected for lactate in sweat (1-20 mM), with appropriate sensitivity (-12.5 ± 0.53 nA mM-1), shows an acceptable response time (<90 s), and the influence of changes in pH, temperature, and flow rate are neglectable. Also, the sensor is analytically suitable with regard to reversibility, resilience, and reproducibility. The sensing device is validated through a relatively high number of on-body tests performed with elite athletes cycling and kayaking in controlled environments. Correlation outcomes between sweat lactate and other physiological indicators typically accessible in sports laboratories (blood lactate, perceived exhaustion, heart rate, blood glucose, respiratory quotient) are also presented and discussed in relation to the sport performance monitoring capability of continuous sweat lactate.

In-situ mechanochemically tailorable 2D gallium oxyselenide for enhanced optoelectronic NO2 gas sensing at room temperature.

The adverse effects of NO2 on the environment and human health promote the development of high-performance gas sensors to address the need for monitoring. Two-dimensional (2D) metal chalcogenides have been considered an emerging group of NO2-sensitive materials, while incomplete recovery and low long-term stability are the two major hurdles for their practical implementation. The transformation into oxychalcogenides is an effective strategy to alleviate these drawbacks, but usually requires multiple-step synthesis and lacks controllability. Here, we prepare tailorable 2D p-type gallium oxyselenide with the thicknesses of 3-4 nm, through a single-step mechanochemical synthesis that combines the in-situ exfoliation and oxidation of bulk crystals. The optoelectronic NO2 sensing performances of such 2D gallium oxyselenide with different oxygen contents are investigated at room temperature, in which 2D GaSe0.58O0.42 exhibits the largest response magnitude of 82.2% towards 10 ppm NO2 at the irradiation of UV, with full reversibility, excellent selectivity, and long term stability for at least one month. Such overall performances are significantly improved over those of reported oxygen-incorporated metal chalcogenide-based NO2 sensors. This work provides a feasible approach to prepare 2D metal oxychalcogenides in a single-step manner and demonstrates their great potential for room-temperature fully reversible gas sensing.

Molecular Mechanism of Nardostachyos Radix et Rhizoma-Agrimoniae Herba in Treatment of Arrhythmia Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma （NRER）-Agrimoniae Herba （AH）， the herbal pair effective in regulating the liver， invigorating Qi， and calming palpitations， in the treatment of premature ventricular contractions （PVCs） by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） combined with relevant literature. GeneCards，Online Mendelian Inheritance in Man（OMIM），and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction （PPI） analysis. Metascape platform was used for Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH （such as quercetin，kaempferol，and acacetin） against PVCs mainly involved tumor necrosis factor （TNF），mitogen-activated protein kinase 1（MAPK1），and protein kinase B1（Akt1）. The potential targets were mainly enriched in 26 signaling pathways，such as pathways in cancer and the advanced glycosylation end product （AGE）-receptor of advanced glycosylation end product（RAGE） signaling pathway. The results of molecular docking showed that the majority of the active components （92.59%） of NRER-AH had good binding activities with the main target proteins TNF，MAPK1，and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels，resist inflammation， and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.

Can Wearable Sweat Lactate Sensors Contribute to Sports Physiology?

The rise of wearable sensors to measure lactate content in human sweat during sports activities has attracted the attention of physiologists given the potential of these "analytical tools" to provide real-time information. Beyond the assessment of the sensing technology per se, which, in fact, has not rigorously been validated yet in controlled conditions, there are many open questions about the true usefulness of such wearable sensors in real scenarios. On the one hand, the evidence for the origin of sweat lactate (e.g., via the sweat gland, derivation from blood, or other alternative mechanisms), its high concentration (1-25 mM or even higher) compared to levels in the blood, and the possible correlation between different biofluids (particularly blood) is rather contradictory and generates vivid debate in the field. On the other hand, it is important to point out that accurate detection of sweat lactate is highly dependent on the procedure used to collect and/or reach the fluid, and this can likely explain the large discrepancies reported in the literature. In brief, this paper provides our vision of the current state of the field and a thoughtful evaluation of the possible reasons for present controversies, together with an analysis of the impact of wearable sweat lactate sensors in the physiological context. Finally, although there is not yet overwhelming scientific evidence to provide an unequivocal answer to whether wearable sweat lactate sensors can contribute to sports physiology, we still understand the importance to bring this challenging question up-front to create awareness and guidance in the development, validation, and implementation of wearable sensors.

Lactate Biosensing for Reliable On-Body Sweat Analysis.

Wearable lactate sensors for sweat analysis are highly appealing for both the sports and healthcare fields. Electrochemical biosensing is the approach most widely used for lactate determination, and this technology generally demonstrates a linear range of response far below the expected lactate levels in sweat together with a high influence of pH and temperature. In this work, we present a novel analytical strategy based on the restriction of the lactate flux that reaches the enzyme lactate oxidase, which is immobilized in the biosensor core. This is accomplished by means of an outer plasticized polymeric layer containing the quaternary salt tetradodecylammonium tetrakis(4-chlorophenyl) borate (traditionally known as ETH500). Also, this layer prevents the enzyme from being in direct contact with the sample, and hence, any influence with the pH and temperature is dramatically reduced. An expanded limit of detection in the millimolar range (from 1 to 50 mM) is demonstrated with this new biosensor, in addition to an acceptable response time; appropriate repeatability, reproducibility, and reversibility (variations lower than 5% for the sensitivity); good resiliency; excellent selectivity; low drift; negligible influence of the flow rate; and extraordinary correlation (Pearson coefficient of 0.97) with a standardized method for lactate detection such as ion chromatography (through analysis of 22 sweat samples collected from 6 different subjects performing cycling or running). The developed lactate biosensor is suitable for on-body sweat lactate monitoring via a microfluidic epidermal patch additionally containing pH and temperature sensors. This applicability was demonstrated in three different body locations (forehead, thigh, and back) in a total of five on-body tests while cycling, achieving appropriate performance and validation. Moreover, the epidermal patch for lactate sensing is convenient for the analysis of sweat stimulated by iontophoresis in the subjects' arm, which is of great potential toward healthcare applications.

A rime ice-inspired bismuth-based flexible sensor for zinc ion detection in human perspiration.

A nature-inspired special structure of bismuth is newly presented as Zn ion sensing layer for high-performance electrochemical heavy metal detection sensor applications. The rime ice-like bismuth (RIBi) has been synthesized using an easy ex situ electrodeposition method on the surface of a flexible graphene-based electrode. The flexible graphene-based electrode was fabricated via simple laser-writing and substrate-transfer techniques. The Zn ion sensing performance of the proposed heavy metal sensor was evaluated by square wave anodic stripping voltammetry after investigating the effects of several parameters, such as preconcentration potential, preconcentration time, and pH of acetate buffer. The proposed RIBi-based heavy metal sensor demonstrated a good linear relationship between concentration and current in the range 100-1600 ppb Zn ions with an acceptable sensitivity of 106 nA/ppb·cm2. The result met the requirements in terms of common human perspiration levels (the average Zn ion concentration in perspiration is 800 ppb). In addition, the heavy metal sensor response to Zn ions was successfully performed in human perspiration samples as well, and the results were consistent with those measured by atomic absorption spectroscopy. Besides, the fabricated Zn ion sensor exhibited excellent selectivity, repeatability, and flexibility. Finally, a PANI-LIG-based pH sensor (measurement range: pH 4-7) was also integrated with the Zn ion sensor to form a single chip hybrid sensor. These results may provide a great possibility for the use of the proposed flexible sensor to realize wearable perspiration-based healthcare systems. Graphical abstract.

The Curvilinear Relationship Between Career Calling and Work Fatigue: A Moderated Mediating Model.

Drawing on the job demands-resources (JD-R) model and event system theory (EST), this study constructed a moderated mediating model to investigate the direct effect of career calling on work fatigue, the mediating effect of role overload, and the moderating effect of COVID-19 event disruption in the above relationships. We administered an online questionnaire to 488 Chinese police officers who participated in frontline work to prevent and control the COVID-19 pandemic. The results showed a U-shaped curvilinear relationship of career calling with physical fatigue, mental fatigue, emotional fatigue, and role overload. Moreover, role overload partially mediated these curvilinear relationships. In addition, COVID-19 event disruption positively moderated the direct curvilinear effect of career calling on role overload, physical fatigue, and emotional fatigue, as well as the first stage of the mediating effect in the relationship between career calling and physical, mental, and emotional fatigue through role overload. Furthermore, the direct U-shaped curvilinear effects and the indirect effects were more significant when COVID-19 event disruption was high.

High-Performance Flexible Electrochemical Heavy Metal Sensor Based on Layer-by-Layer Assembly of Ti3C2Tx/MWNTs Nanocomposites for Noninvasive Detection of Copper and Zinc Ions in Human Biofluids.

A flexible electrochemical heavy metal sensor based on a gold (Au) electrode modified with layer-by-layer (LBL) assembly of titanium carbide (Ti3C2Tx) and multiwalled carbon nanotubes (MWNTs) nanocomposites was successfully fabricated for the detection of copper (Cu) and zinc (Zn) ions. An LBL drop-coating process was adopted to modify the surface of Au electrodes with Ti3C2Tx/MWNTs treated via ultrasonication to fabricate this novel nanocomposite electrode. In addition, an in situ simultaneous deposition of "green metal" antimony (Sb) and target analytes was performed to improve the detection performance further. The electrochemical measurement was realized using square wave anodic stripping voltammetry (SWASV). Moreover, the fabricated sensor exhibited excellent detection performance under the optimal experimental conditions. The detection limits for Cu and Zn are as low as 0.1 and 1.5 ppb, respectively. Furthermore, Cu and Zn ions were successfully detected in biofluids, that is, urine and sweat, in a wide range of concentration (urine Cu: 10-500 ppb; urine Zn: 200-600 ppb; sweat Cu: 300-1500 ppb; and sweat Zn: 500-1500 ppb). The fabricated flexible sensor also possesses other advantages of ultra-repeatability and excellent stability. Thus, these advantages provide a great possibility for the noninvasive smart monitoring of heavy metals in the future.

MoS2-Decorated Laser-Induced Graphene for a Highly Sensitive, Hysteresis-free, and Reliable Piezoresistive Strain Sensor.

Advancement of sensing systems, soft robotics, and point-of-care testing requires the development of highly efficient, scalable, and cost-effective physical sensors with competitive and attractive features such as high sensitivity, reliability, and preferably reversible sensing behaviors. This study reports a highly sensitive and reliable piezoresistive strain sensor fabricated by one-step carbonization of the MoS2-coated polyimide film to obtain MoS2-decorated laser-induced graphene. The resulting three-dimensional porous graphene nanoflakes decorated with MoS2 exhibit stable electrical properties yielding a reliable output for longer strain/release cycles. The sensor demonstrates high sensitivity (i.e., gauge factor, GF ≈1242), is hysteresis-free (∼2.75%), and has a wide working range (up to 37.5%), ultralow detection limit (0.025%), fast relaxation time (∼0.17 s), and a highly stable and reproducible response over multiple test cycles (>12 000) with excellent switching response. Owing to the outstanding performances of the sensor, it is possible to successfully detect various subtle movements ranging from phonation, eye-blinking, and wrist pulse to large human-motion-induced deformations.

A highly stretchable and conductive 3D porous graphene metal nanocomposite based electrochemical-physiological hybrid biosensor.

Recently, highly stretchable and flexible electrodes essential for wearable electronic devices has been reported. However, their electrical resistances are high, the fabrication processes are complicated and involve a high cost, and deformations such as stretching can lead to the degradation on electrical performance. To address these issues, a novel fabrication process (both inexpensive and simple) for the highly stretchable and conductive electrodes using well patterned 3D porous laser-induced graphene silver nanocomposite was developed. The fabricated electrode exhibited a high, uniform electrical conductivity even under mechanical deformations. Addition of platinum and gold nanoparticles (PtAuNP) on the 3D porous LIG greatly improved the electrochemical performance for wearable glucose sensor applications. The fabricated glucose sensor exhibited low detection limit (5 µM), and acceptable detection range from 0 to 1.1 mM (covers the glucose range in sweat), and high linearity (0.99). In addition, the fabricated pH sensor also exhibited a linear response (66 mV/pH) at the range from 4 to 7. This work successfully demonstrates the potential of this novel fabrication technique and stretchable LIG metal nanocomposite for wearable electrochemical-physiological hybrid biosensors.

Wearable, robust, non-enzymatic continuous glucose monitoring system and its in vivo investigation.

Electroplating of nanoporous Pt (nPt) induces an extremely strong tensile stress, which results in the exfoliation of nPt on flexible polymer substrate despite plasma treatment to improve adhesion. Here, we overcame this challenge by modifying flexible stainless-steel, and developed wearable, robust, flexible, and non-enzymatic continuous glucose monitoring system. The flexible stainless-steel was highly effective in improving the adhesion between the metal layer and substrate. The developed wireless system included electrochemical analysis circuits, a microcontroller unit, and a wireless communication module. Finally, we evaluated the continuous glucose monitoring system through two animal testing, by implanting into subcutaneous tissue and measuring interstitial fluid (ISF) glucose values at 5-15-min intervals. Comparison of the measured ISF glucose with blood glucose determined by the Clarke error grid analysis showed that 82.76% of the measured glucose was within zone A. Furthermore, the wearable glucose sensor exhibited bio-compatible to implant through various bio-compatibility tests.

A wearable electrochemical glucose sensor based on simple and low-cost fabrication supported micro-patterned reduced graphene oxide nanocomposite electrode on flexible substrate.

In this study, a reduced graphene oxide (rGO)-based nanostructured composite working electrode of high quality was successfully microfabricated and micro-patterned on a flexible polyimide substrate using simple low-cost fabrication processes. Gold and platinum alloy nanoparticles were electrochemically deposited onto the microfabricated rGO surface and chitosan-glucose oxidase composites were integrated onto the modified surface of the working electrode to develop a human sweat-based wearable glucose sensor application. The fabricated biosensor exhibited excellent amperometric response to glucose at a detection range of 0-2.4 mM (covers the glucose range in sweat), with a sensitivity of 48 µA/mMcm2, a short response time (20 s), and high linearity (0.99). The detection limit for glucose was calculated as 5 µm. The human sweat/mixing glucose samples initially used for testing indicated acceptable detection performance and stability for low glucose concentrations. These results confirm that the proposed nanostructured composite flexible working electrode and fabrication process are highly promising for application as human sweat-based electrochemical glucose sensors.

A Fully Integrated and Miniaturized Heavy-metal-detection Sensor Based on Micro-patterned Reduced Graphene Oxide.

For this paper, a fully integrated and highly miniaturized electrochemical sensor was designed and fabricated on a silicon substrate. A solvothermal-assisted reduced graphene oxide named "TRGO" was then successfully micro-patterned using a lithography technique, followed by the electrodeposition of bismuth (Bi) on the surface of the micro-patterned TRGO for the electrochemical detection of heavy metal ions. The fully integrated electrochemical micro-sensor was then measured and evaluated for the detection of cadmium and lead-heavy metal ions in an acetic-acid buffered solution using the square wave anodic stripping voltammetry (SWASV) technique. The fabricated micro-sensor exhibited a linear detection range of 1.0 µg L(-1) to 120.0 µg L(-1) for both of the metal ions, and detection limits of 0.4 µg L(-1) and 1.0 µg L(-1) were recorded for the lead and cadmium (S/N = 3), respectively. Drinking-water samples were used for the practical assessment of the fabricated micro-sensor, and it showed an acceptable detection performance regarding the metal ions.

Complete mitochondrial genome of the Nigeria-Cameroon chimpanzee, Pan troglodytes ellioti (Primates: Hominidae).

Chimpanzees are especially suited to teach us about ourselves, both in terms of their similarities and differences with human, and such important similarities and differences have also been noted for the incidence and severity of several major human diseases. In the present work, we report the entire mitochondrial genome of the Nigeria-Cameroon chimpanzee (Pan troglodytes ellioti) for the first time. Results shows that this mitogenome is 16,559 bp long and consists of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 putative non-coding region (D-loop region). The genomic organization and gene order are the same as other Chimpanzees. The whole nucleotide base composition is 31.1% of A, 30.7% of C, 12.9% G, and 25.3% T, with a slight A+T bias of 56.4%. Most of the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes. The complete mitochondrial genome sequence reported here provides useful genetic information for P. t. ellioti, and will further contribute to the comparative genomics studies in primates.