Sensitive Response Research Articles

Correlating autonomic physiology with symptoms of autonomic dysreflexia after spinal cord injury

AbstractBackgroundIndividuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex sensitivity and increased vascular responsiveness.ObjectiveTo evaluate the relationship between baroreflex and blood vessel sensitivity with AD symptoms.DesignCase control.SettingTertiary academic center.Patients14 individuals with SCI, 17 matched uninjured controls.InterventionsAll participants quantified AD symptoms using the Autonomic Dysfunction Following SCI (ADFSCI)‐AD survey. Participants received three intravenous phenylephrine boluses, reproducibly increasing systolic blood pressure (SBP) 15–40 mmHg. Continuous heart rate (R‐R interval, ECG), beat‐to‐beat blood pressures (Finapres), and popliteal artery flow velocity were recorded. Vascular responsiveness (α1 adrenoreceptor sensitivity) and heart rate responsiveness to increased SBP (baroreflex sensitivity) were calculated.Main Outcome MeasuresBaroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2‐minute area under the curve and change in vascular resistance.ResultsSCI and control cohorts were well matched with mean age 31.9 and 29.6 years (p = .41); 21.4% and 17.6% female, respectively. Baseline MAP (p = .83) and R‐R interval (p = .39) were similar. ADFSCI‐AD scores were higher following SCI (27.9 ± 22.9 vs. 4.2 ± 2.9 in controls, p = .002). To quantify SBP response, MAP area under the curve was normalized to dose/body weight. Individuals with SCI had significantly larger responses (0.26 ± 0.19 mmHg*s/kg*μg) than controls (0.06 ± 0.06 mmHg*s/kg*μg, p = .002). Similarly, leg vascular resistance increased after SCI (24% vs. 6% to a normalized dose, p = .007). Baroreflex sensitivity was significantly lower after SCI (15.0 ± 8.3 vs. 23.7 ± 9.3 ms/mmHg, p = .01). ADFSCI‐AD subscore had no meaningful correlation with vascular responsiveness (R2 = 0.008) or baroreflex sensitivity (R2 = 0.092) after SCI.ConclusionsAlthough this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, contrary to our hypothesis these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms is needed to explain why some individuals with SCI develop symptoms.

Self-powered ultraviolet position-sensitive detectors based on PrNiO3/Nb-doped SrTiO3 p–n junctions

Position-sensitive detectors based on the lateral photovoltaic effect have been widely used in optical engineering for the measurement of position, distance, and angles. However, self-powered ultraviolet position-sensitive detectors with high sensitivity and fast response are still lacking due to the difficulty associated with the fabrication of p-type wide bandgap semiconductors, which hinders their further design and enhancement. Here, the influence of band structures and interfacial transport properties on the performance of self-powered ultraviolet position-sensitive detectors based on PrNiO3/Nb:SrTiO3p–n junctions is systematically investigated. Large position sensitivity and fast relaxation time of the lateral photovoltaic effect were observed up to 400 K in the perovskite-based ultraviolet position-sensitive detectors. Hall effect measurements revealed that the transport of photoexcited carriers occurs mainly through the interface of the PrNiO3/Nb:SrTiO3 junctions, resulting in a fast response and a stable photovoltaic effect. This study presents insights and avenues for designing self-powered perovskite oxide ultraviolet position-sensitive detectors with enhanced photoelectric performance.

Integration of silver nanostructures in wireless sensor networks for enhanced biochemical sensing.

Integrating noble metal nanostructures, specifically silver nanoparticles, into sensor designs has proven to enhance sensor performance across key metrics, including response time, stability, and sensitivity. However, a critical gap remains in understanding the unique contributions of various synthesis parameters on these enhancements. This study addresses this gap by examining how factors such as temperature, growth time, and choice of capping agents influence nanostructure shape and size, optimizing sensor performance for diverse conditions. Using silver nitrate and sodium borohydride, silver seed particles were created, followed by controlled growth in a solution containing additional silver ions. The size and morphology of the resulting nanostructures were regulated to achieve optimal properties for biochemical sensing in wireless sensor networks. Results demonstrated that embedding these nanostructures in Polyvinyl Alcohol (PVA) matrices led to superior stability, maintaining 93% effectiveness over 30days compared to 70% in Polyethylene Glycol (PEG). Performance metrics revealed significant improvements: reduced response times (1.2ms vs. 1.5ms at zero analyte concentration) and faster responses at higher analyte levels (0.2ms). These outcomes confirm that higher synthesis temperatures and precise shape control contribute to larger, more stable nanostructures.The enhanced stability and responsiveness underscore the potential of noble metal nanostructures for scalable and durable sensor applications, offering a significant advancement over current methods.

Enhancing Selectivity of Two‐Dimensional Materials‐Based Gas Sensors

AbstractTwo‐dimensional (2D) materials have emerged as promising candidates for gas sensing applications due to their exceptional electrical, structural, and chemical properties, which enable high sensitivity and rapid response to gas molecules. However, despite their potential, 2D material‐based gas sensors face a significant challenge in achieving adequate selectivity, as many sensors respond similarly to multiple gases, leading to cross‐sensitivity and inaccurate detection. This review provides a comprehensive overview of the recent advancements for improving the selectivity of 2D gas sensors. It explores material modification strategies, such as functionalizing the sensing components and tuning adsorption dynamics, to enhance selective gas interactions. Engineering approaches, including field‐effect modulation and sensor array design, are also discussed as effective methods to fine‐tune sensor performance. Additionally, the integration of machine learning (ML) algorithms is highlighted for their potential to differentiate among multiple analytes. Prospects for further improving selectivity through material optimization, sensor calibration, and drift compensation are explored, along with the incorporation of smart sensing systems into the Internet of Things (IoT). This review outlines key objectives and strategies that pave the way for next‐generation gas sensors with enhanced selectivity, reliability, and versatility, poised to impact a wide range of applications from environmental monitoring to industrial safety.

A Nitrate/Nitrite Biosensor Designed with an Antiterminator for In Vivo Diagnosis of Colitis Based on Bacteroides thetaiotaomicron.

Bacteroides thetaiotaomicron is a common microorganism in the human gut that has been linked to health benefits. Furthermore, it is an emerging synthetic biology chassis with the potential to be modified into diagnostic or therapeutic engineered probiotics. However, the absence of biological components limits its further applications. In this study, we developed an antiterminator microbial whole-cell biosensor (MWCB) based on B. thetaiotaomicron. The antiterminator-based element allows the chassis to detect colitis in mice by responding to nitrate and nitrite in an inflammatory environment. In particular, the nitrate/nitrite-inducible promoter was obtained by combining the constitutive promoter with the inducible terminator. Subsequently, the promoter and RBS were replaced to optimize a sensitive and specific response to nitrate/nitrite. A preliminary in vitro assessment was conducted to ascertain the functionality of the biosensor. Its in vivo sensing ability was evaluated in a chemically induced mouse model of ulcerative colitis (UC). The results demonstrated that the MWCB exhibited a robust response to colitis, with a notable positive correlation between the intensity of the response and the level of inflammation. This novel sensing element may provide a new avenue for the development of components for unconventional chassis, like B. thetaiotaomicron. It will also facilitate the development of engineered probiotics based on B. thetaiotaomicron, thereby providing patients with a wider range of medical treatment options.

Effects of Polystyrene Microplastic Exposure on Liver Cell Damage, Oxidative Stress, and Gene Expression in Juvenile Crucian Carp (Carassius auratus)

A considerable quantity of microplastic debris exists in the environment and the toxicity of these materials has a notable impact on aquatic ecosystems. In this paper, 50–500 µm polystyrene microplastics (exposure concentrations were 200 µg/L, 800 µg/L, and 3200 µg/L concentrations) were selected to study the effects of polystyrene microplastics (PS-MPs) on cell morphology, detoxification enzyme activity, and mRNA expression in the liver tissues of crucian carp juveniles. The results demonstrated that: (1) Different concentrations of PS-MPs cause varying degrees of pathological and oxidative damage to liver tissue cells of crucian carp. The higher the concentration of microplastics, the lower the antioxidant enzyme (CAT, GST, SOD) activity and the greater the tissue cell damage. These results demonstrate a typical dose–effect relationship. (2) Principal component analysis and Spearman’s correlation analysis demonstrated that four components, namely glutathione S-transferase (GST) and its related genes (GSTpi, GSTα), along with catalase (CAT), contributed the most to the observed outcome. These four components demonstrated a relatively high level of responsiveness to PS-MP exposure and can be employed as ecotoxicological indicators of microplastics. (3) This experiment evaluated five genes in three treatments, which found that PS-MPs had different effects on gene expression in the liver and the tested genes were involved in different response pathways associated with virulence. In this study, the toxicity of PS-MPs to crucian carp was determined at the cellular, protein, and mRNA expression levels, and combined with principal component analysis and correlation analysis to identify response sensitivity indicators that provide a scientific basis for ecological risk assessment and the safe use of microplastics.

Ion Sensing via Modulation of Charge Transfer in Donor-pi-Acceptor Molecules: Structure, Mechanism & Photophysical Aspects.

This review article highlights the importance of novel charge transfer (CT) sensing approach for the detection of ions which are crucial from environmental and biological point of view. The importance, principles of charge transfer, ion sensing, its different types, and its basic process will all be covered here. The strategy has been reported with enormous sensitivity and fast signaling response owing to the fact that strong electronic connection communication exists between donor (D) and acceptor (A) part. Important discoveries made since 2010 will be examined. Herein, we will showcase the binding constants, conditions employed for sensing, and limit of detection of crucial ions via CT based sensors that researchers have bough forth for real-time applications. Additionally, the focus will be on the mechanistic aspects and signaling response as a result of the interaction between ion and sensor molecule.

Translation and validation of the 8-item contact lens dry eye questionnaire (CLDEQ-8) among Chinese soft contact lens wearers.

To develop a Chinese version of the 8-item Contact Lens Dry Eye Questionnaire (CLDEQ-8) with cross-cultural adaption and clinical validation among soft contact lens wearers (SCL) in China. The translation and adaptation of the Chinese CLDEQ-8 (C-CLDEQ-8) followed a rigorous methodological process based on cross-cultural research guidelines consisting of three main phases: 1) forward and backward translation of original CLDEQ-8 into Chinese, 2) cross-cultural adaptation performed by medical advising committee, and 3) clinical validation and repeatability test of the translated questionnaire on Chinese SCL wearers. Rasch analysis was also performed to investigate the psychometric properties of C-CLDEQ-8. 134 experienced SCL wearers aged 18-45 completed the C-CLDEQ-8. C-CLDEQ-8 score was linearly related to the overall opinion of SCLs (beta=2.16, p=0.002), gestalt eye dryness response (beta=2.90, p<0.001), and sensitivity response (beta=1.83, p=0.001). The questionnaire showed excellent test-retest repeatability with an intra-class correlation coefficient (ICC) of 0.95 and great internal consistency with a Cronbach's alpha of 0.83. The corrected index of homogeneity for each item was more significant than 0.5. In Rasch analysis, the infit and outfit values for eight items were all within 0.6-1.4, suggesting a good fit for the Rasch model. Martin-Löf test result indicated that the Rasch model was unidimensional (p=1.0). Item characteristics curves suggested combining categories 3-4 and 5-6 in item 5 of C-CLDEQ-8. This study produced a Chinese version of CLDEQ-8 with great validity and reliability and proved capable of evaluating SCL-related symptoms.

Regulation of TADF by Internal and External Heavy Atom Effect in D-A MOF for Heterocrystal based Temperature-Compensated Photonic Device.

The application of temperature-compensated photonic device is hampered by poor accuracy and overly simplistic functions of propagation in photonic integrated circuits (PICs) field. Herein, we report a new library of donor-acceptor metal-organic framework (D-A MOF) with thermally activated delayed fluorescence (TADF) and the fabricating of temperature-compensated photonic device by virtue of the unique temperature response character of TADF emitters. Highly tunable through-space charge transfer (TSCT) of TADF was realized within the D-A MOFs through a novel strategy that synergistically combines the internal heavy atom effect (HAE) with an external HAE, induced by the incorporation of heavy atoms into different components, achieving the regulable photophysical indicators including adjustable PL wavelength (534 to 592 nm) and surging quantum yield (5.02%-47.39%). Further investigation of the impact of external HAE on TADF was conducted through crystal structures and Hirshfeld surface plots of four D-A regimes featuring substituent-based linkers. Notably, temperature-compensated photonic device based on heterocrystal was fabricated through integrating D-A MOFs with contrary temperature response. The emission signal output of the heterojunction remained nearly stable in 215 K to 295 K range, highlighting the promising potential application of TADF D-A MOF featuring sensitive temperature response in PICs field.

Construction of UCST-Responsive Claw-Like Polysulfobetaines for Efficient Capture of Cellulase.

The high cost of enzymatic glycolysis has seriously restricted the industrialization of lignocellulose-based sugar platform technology. Recovering and recycling cellulase can reduce the cost. Here, a thermo-responsive claw-type polysulfobetaine (PSPA) was constructed for hydrophobic grasping and efficient recycling of cellulase. Compared with the linear sulfobetaine homopolymer (PSPE), PSPA had more sensitive temperature response and strong cellulase recovery ability. PSPE-3 (Mw=355.1 kDa) was added to the hydrolysis system of corncob residue (CCR) (50 °C), at 0.4 mass ratio of PSPE-3 to cellulase, and after enzymatic hydrolysis, 50% of the cellulase was saved when cooling to 25 °C. But only 0.05 times PSPA-1 (Mw=30.0 kDa) was added to the CCR system, and 70% of the cellulase was saved when cooling to 25 °C. This work presents a claw shaped protein-capture agent, polysulfobetaine for capturing cellulase, which is of great significance to reduce the lignocellulosic hydrolysis cost, and efficiently separate enzyme proteins.

Construction of GOx-loaded metal organic frameworks antibacterial composite hydrogels for skin wound healing.

Bacterial infections and inflammation severely impede wound healing. Here, we developed a zwitterionic hydrogel incorporating MOF/GOx for pH-responsive, controlled drug release. The multifunctional hydrogel embedded with MOF/GOx was successfully prepared through the Schiff base reaction between the copolymer poly[(2-methacryloyloxyethyl phosphorylcholine)-co-(4-formylphenyl methacrylate)] (PMF) and the branched polyethylenimine (PEI) modified by the zwitterionic monomer ((4-hydroxyphenyl)sulfonyl)(4-(trimethylammonio)butanoyl)amide (AB), which possessed excellent injectable and self-healing ability, a highly sensitive and reversible responsiveness to pH changes, and good biocompatibility. Moreover, the MOF/GOx-PP composite hydrogel under exposure to a slightly acidic environment would rupture, and the slowly released MOF/GOx triggered a cascade-catalyzed reaction that could inhibit and kill Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and, simultaneously, mouse experiments indicated that the wound healing rate showed 93 % wound closure in 7 days compared to 67 % with controls. The multifunctional antibacterial hydrogel has immense potential as a dressing in the treatment of infected wounds.

Electro-polymerization of modified carbon paste sensor for detecting azithromycin.

Azithromycin (AM) is one of the prescribed drugs in pandemic medication treatment which has paid great attention. We developed in this study a simply modified carbon paste electrode (CPE) to detect AM using poly-threonine (PT). PT or similar polymers are used as carriers to enhance the delivery and effectiveness of AM. The work was characterised via Cyclic Voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). We take into consideration the effects of pH, scan rate, accumulation time, interference, and calibration curve.A very sensitive response to the oxidation of 1.0 mM from AM in phosphate buffer solution (PBS) over a pH range of 5.0 to 10.0 was observed using the developed poly-threonine carbon paste electrode (PTCPE). The impact of different AM concentrations was investigated resulting in a detection limit of 0.32 µM and a quantification limit of 1.07 µM at PBS (pH 7.4). Finally, the recently used electrode realized acceptable sensitivity and consistency for AM detection in pharmaceutical drugs.

Novel Electrochemiluminescence Sensor for Dopamine Detection Based on Perylene Diimide/CuO Nanomaterials.

Dopamine (DA) is an important catecholamine neurotransmitter and its abnormal concentration is closely related to diseases such as hypertension, Parkinson's disease and schizophrenia. Due to the advantages of high sensitivity and fast response for electrochemiluminescence (ECL), developing ECL sensors for detecting DA was very critical in clinical diagnosis. ECL resonance energy transfer (ECL-RET) was an effective signaling mechanism. However, the shortage of highly efficient ECL-RET pairs impeded the development of DA sensors. Herein, methyl-modified perylene diimide derivative (PDI-CH3) self-assembly nanorod materials as luminophores and CuO nanomaterials as acceptors were integrated into nanocomposites. An obvious ECL-RET was found in PDI-CH3/CuO nanocomposites. After PDI-CH3/CuO nanocomposites were treated with DA, a large increase in ECL intensity was observed. Then, PDI-CH3/CuO nanocomposites were taken as an ECL platform to detect DA. This ECL sensor exhibited a linear response to DA from 10-12 M to 10-8 M with a limit of detection of 0.20 pM. Compared with other sensors for DA detection, the constructed ECL sensor exhibited higher sensitivity. In addition, the novel ECL sensor in this work showed good practicability in a human serum sample.

Zero-Crosstalk Tumor-Targeting Ratiometric Near-Infrared γ-Glutamyltranspeptidase Probe for Fluorescent-Guided Surgical Resection of Orthotopic Hepatic Tumor.

The challenge of "false positive" signals significantly complicates tumor localization and surgical resection, which are pivotal for successful tumor surgeries. Therefore, the development of a method for preoperative tumor localization and intraoperative margin determination holds considerable promise for improving surgical outcomes. In this study, a zero-crosstalk ratiometric tumor-targeting near-infrared (NIR) fluorescent probe was developed for precise cancer diagnosis and intraoperative navigation via NIR fluorescence imaging. This probe integrates a tumor-targeting moiety that selectively homes in on hepatocellular carcinoma cells and exhibits a highly sensitive ratiometric response to γ-glutamyltranspeptidase (GGT), characterized by a substantial emission shift from 830 to 650 nm. This unique NIR ratiometric emission property significantly enhances its effectiveness in early diagnosis and imaging-guided surgery resection. Furthermore, this zero-crosstalk probe successfully monitors GGT activity in blood, cells, and in vivo, endowing its potential for early cancer diagnosis in the clinic. Due to its efficient targeting and sensitive in situ response to GGT in both subcutaneous tumors and orthotopic hepatic tumors, the probe exhibits accurate detection capability for hepatic tumors. Additionally, by leveraging zero-crosstalk ratiometric NIR fluorescence imaging, this tumor-targeting probe can serve as a sprayable tool for delineating tumor margins with precision, thereby furnishing real-time intraoperative imaging guidance during tumor resection surgery.

Designing Hybrid Plasmonic Superlattices with Spatially Confined Responsive Heterostructural Units.

Plasmonic superlattices enable the precise manipulation of electromagnetic fields at the nanoscale. However, the optical properties of static lattices are dictated by their geometry and cannot be reconfigured. Here, we present a surface-interface engineered plasmonic superlattice with confined polyelectrolyte-functionalized metal-organic framework (MOF) hybrid layers to tune plasmon resonance for ultrafast chemical sensing. The surface lattice resonance frequency in the visible spectrum was achieved using electron-beam lithography with a humidity-responsive polyelectrolyte brush grafted onto the thiol-initiator-modified gold nanoparticle surface through atom transfer radical polymerization. An MOF thin film was assembled on the polyelectrolyte-functionalized gold nanoparticle lattice via a layer-by-layer immersion. Surface lattice resonance was observed without additional matched dielectric environment around the NPs, and the resonance frequency was tuned by adjusting the thickness and refractive index of the polyelectrolyte layer. Furthermore, high chemical sensitivity and ultrafast response were achieved due to the coherence between the MOFs and polymer layers.

Polyester/cotton fabrics fire alarm sensors with sensitive fire warning response and excellent flame retardancy

Intelligent fire alarm textiles are beneficial for prevent the occurrence of fire. However, the sensitivity and sustained response time of intelligent fire alarm textiles will directly affect fire losses. In this study, intelligent fire alarm polyester/cotton blend fabrics (PCFs) with excellent flame retardancy were prepared by construction of GO@PA/CNTs@CS organic and inorganic composite coating containing phytic acid (PA), chitosan (CS), graphene oxide (GO) and carbon nanotubes (CNTs). GO@PA/CNTs@CS coating greatly enhanced the flame retardancy of PCFs to obtain a LOI value of 30%, and it also endowed PCFs with self-extinguishing property. The fire hazard of PCF coated with GO@PA/CNTs@CS was significantly reduced with 40.5% reduction of peak heat release rate (pHRR) and 72.3% reduction of total heat release (THR). The fire alarm trigger time of GO@PA/CNTs@CS coated PCF was 1.5s, showing the super-fast fire warning response. The fire alarm response signal can still be sent out even when the coated PCF was burnt in a fire for over 600s, showing the long-term fire alarm response property. This study provides the experimental basis to prepare intelligent fire alarm textiles with sensitive fire warning response property and excellent flame retardancy.

Intelligent antibacterial coatings based on sensitive response and periodic fast drug release for long-term defense against corrosion induced by sulfate-reducing bacteria.

Pitting corrosion caused by sulfate-reducing bacteria (SRB) significantly shortens the lifespan of metallic pipelines. Antibacterial coatings containing S2--responsive drug-loaded nanocontainers represent a promising method to mitigate SRB corrosion. However, the challenge of balancing rapid bactericide release with continuous antibacterial effect limits their practical application. In this study, a S2- and pH dual-responsive periodic drug release system was developed based on raspberry-like mesoporous silica intelligent nanocontainers (BAC-RMSNs@Cu-BTA) loaded with bactericide benzalkonium chloride (BAC) and blocked by copper-benzotriazole nano valves (Cu-BTA). When S2- concentration exceeded 0.5mM or pH fell below 6.3, the intelligent nanocontainers accelerated drug release. Under simultaneous S2- and pH stimulation, the drug release rate was increased by 91%, compared to isolated S2- stimulation. The sustained release duration exceeded 384h, which was more than twice that of existing S2--responsive nanocontainers. The reversible dissociation-complexation transition of Cu-BTA nano valves and the adsorption effect of the raspberry structure facilitated an inhibition of drug release after the stimulation disappeared, thereby enabling cyclic drug release and extending the antibacterial duration. The epoxy coating embedded with BAC-RMSNs@Cu-BTA showed excellent repeatable sterilization, long-term antibacterial adhesion and corrosion medium barrier ability in the SRB environment. Based on active intelligent sterilization and passive physical barrier effects, the composite coating's resistance to SRB corrosion in the simulated internal environment of pipelines was 14.6 times that of coating containing BAC-RMSNs. This study aims to provide valuable insights for the design of innovative long-acting antibacterial coatings.

ColorNet: An AI-based framework for pork freshness detection using a colorimetric sensor array.

Pork freshness is crucial for flavour, nutrition and consumer health. The current colorimetric sensor array (CSA) detection systems face challenges related to high sensor development costs, low recognition accuracy and limitations in the platform use. Herein, we developed a CSA and ColorNet framework to detect pork freshness. The 53-point CSA was designed by selecting sensitised pH indicators and aldehyde/ketone indicators. To optimize the sensor, the Euclidean distance method was used to identify 24 array points with dyes that exhibited more sensitive responses. The ColorNet captured the color information of pork freshness, allowing real-time detection with a 99.5% accuracy. For practical deployment and mobile applications, a refined 12-point CSA was developed using gradient activation mapping, maintaining a 99% recognition rate, which is comparable with the 24-point CSA. The proposed CSA and model ensure consumer health and safety, providing strong technical support for quality monitoring and control in the pork industry.

The stoichiometry of the α4β2 neuronal nicotinic acetylcholine receptors determines the pharmacological properties of the neonicotinoids, and recently introduced butenolide and sulfoximine.

Although neonicotinoids were considered safe for mammals for many decades, recent research has proven that these insecticides can alter cholinergic functions by interacting with neuronal nicotinic acetylcholine (ACh) receptors (nAChRs). One such receptor is the heteromeric α4β2 nAChR, which exists under two different stoichiometries: high sensitivity and low sensitivity α4β2 nAChRs. To replace these insecticides, new classes of insecticides have been developed, such as, sulfoximine, sulfoxaflor, and the butanolide, flupyradifurone. In this study, we injected Xenopus laevis oocytes with 1:10 and 10:1 α4:β2 subunit RNA ratios, in order to express the high (α4)2(β2)3 and low sensitivity (α4)3(β2)2 nAChRs. Using the two-electrode voltage-clamp technique, we found that the low sensitivity (α4)3(β2)2 nAChRs were activated by all tested insecticides, whereas the high sensitivity (α4)2(β2)3 nAChR was only activated by ACh. Imidacloprid, sulfoxaflor and flupyradifurone confirmed their agonist effects by reducing the responses to the ACh EC80 concentrations, for both low (α4)3(β2)2 and high sensitivity (α4)2(β2)3 stoichiometries. Clothianidin only inhibited ACh responses of the low sensitivity (α4)3(β2)2 stoichiometry. Mutation E226P in the α4 subunit of the low sensitivity (α4)3(β2)2 receptors inhibits the agonist potency of imidacloprid and flupyradifurone, whereas mutation L273T in the high sensitivity (α4)2(β2)3 nAChR leads to activation by all insecticides. Major agonist effects were found with the double mutation of the E226P in the α4 subunit, and the L273T in the β2 subunit of the high sensitivity (α4)2(β2)3 stoichiometry.

Subcomponent analysis of the directional sensitivity of dynamic cerebral autoregulation.

The origin of the directional sensitivity (DS) of dynamic cerebral autoregulation (dCA) is not known. In 140 healthy participants (67 male, 27.5 ± 6.1 yr old), middle cerebral artery velocity (MCAv, transcranial Doppler), arterial blood pressure (ABP, Finometer), and end-tidal CO2 (EtCO2, capnography) were recorded at rest. Critical closing pressure (CrCP) and resistance-area product (RAP) were obtained for each cardiac cycle, as well as mean MCAv and ABP (MAP). The integrated positive and negative derivatives of MAP (MAP+D and MAP-D, respectively) were used as simultaneous inputs to an autoregressive moving average model to generate two distinct MCAv step responses. Similar models allowed the estimation of corresponding MAP-CrCP and MAP-RAP responses to step changes in MAP+D and MAP-D. The strength of DS (ΔDS) was expressed by the difference in mean values of the step responses for the time interval 12-18 s. ΔDS was significant for MCAv (8.5 ± 46.9% vs. 26.7 ± 42.0%, P < 0.001) and RAP (-93.9 ± 48.1 vs. -74.5 ± 43.0%, P < 0.001), respectively, for MAP+D and MAP-D inputs, but not for CrCP (2.2 ± 48.1% vs. 0.72 ± 42.9%, P = 0.76). Compared with males, female participants had higher MCAv (63.9 ± 15.6 cm/s vs. 55.4 ± 12.9 cm/s, P < 0.001) but lower EtCO2 (P < 0.001) and RAP (P = 0.015). Sex did not influence ΔDS for any of the three-step responses. The presence of directional sensitivity in the RAP, but not in the CrCP transfer function, suggests that the origin could be solely myogenic, without metabolic involvement.NEW & NOTEWORTHY The directional sensitivity of the cerebral blood velocity response to a sudden change in mean arterial blood pressure (MAP) is mediated by the resistance-area product, without involvement from the cerebral critical closing pressure. The reduced amplitude of MAP spontaneous fluctuations at rest suggests that it is less likely that directional sensitivity has origins in the sympathetic control of cerebral blood vessels, thus generating the need to consider other alternatives.